An Explicative Review on the Current Advancement in Schiff Base-Metal
Complexes as Anticancer Agents Evolved in the Past Decade: Medicinal
Chemistry Aspects

Dipanjan      Karati; Swarupananda      Mukherjee; Souvik      Roy
doi:10.2174/1573406419666230707105221
Abstract

In the recent era, developments in the field of bio-inorganic chemistry have improved interest in Schiff base complexes (imine scaffolds) for their pharmacological excellence in different areas. Schiff bases are a kind of synthetic molecule that is synthesized by the condensation reaction between a 1o amine and a carbonyl compound. Imine derivatives are also acknowledged for their ability to form complexes with several metals. Due to their wide range of biological activities, they have acquired prominence in the therapeutic and pharmaceutical industries. Inorganic chemists have continued to be intrigued by the vast range of uses of these molecules. Many of them are also thermally stable and have structural flexibility. Some of these chemicals have been discovered to be beneficial as clinical diagnostic agents as well as chemotherapeutic agents. Because of the flexibility of the reactions, these complexes have a wide range of characteristics and applications in biological systems. Anti-neoplastic activity is one of them. This review attempts to draw attention to the most notable examples of these novel compounds, which have excellent anticancer activity against different cancers. The synthetic scheme of these scaffolds, their metal complexes, and the explanation of their anticancer mechanism reported in this paper lead the researchers to design and synthesize more target-specific Schiff base congeners with little or no side effects in the future.
Keywords: Schiff base, synthetic strategy, schiff base metal-catalyzed complexes, coordination chemistry, anticancer activity, imine.
« Previous
Graphical Abstract

[1]
Arulmurugan, S.; Kavitha, H.P.; Venkatraman, B.R. Biological activities of schiff base and its complexes: A review. Rasayan J. Chem.,  2010, 3(3), 385-410.

[2]
Siddappa, K.; Mayana, N.S. Synthesis, spectroscopic characterization, and biological evaluation studies of 5-Bromo-3-(((hydroxy-2- methylquinolin-7-yl) methylene)hydrazono)indolin-2- one and Its Metal (II) Complexes. Bioinorg. Chem. Appl.,  2014, 2014, 483282.
 [http://dx.doi.org/10.1155/2014/483282] [PMID: 25371658]

[3]
Woźniczka, M.; Sutradhar, M.; Pombeiro, A.J.L.; Świątek, M.; Pająk, M.; Gądek-Sobczyńska, J.; Chmiela, M.; Gonciarz, W.; Pasternak, B.; Kufelnicki, A. Equilibria in aqueous cobalt(II)— reduced schiff base N-(2-hydroxybenzyl)alanine system: Chemical characterization, kinetic analysis, antimicrobial and cytotoxic properties. Molecules,  2020, 25(15), 3462.
 [http://dx.doi.org/10.3390/molecules25153462] [PMID: 32751474]

[4]
Ibrahim, F.M.; Jassim, A.H.; Muhyedeen, B.R.J. Synthesis and AB initio study of biologically important thioamide; LAP LAMBERT Academic Publishing: Germany, 2018, p. 116.

[5]
Gavalyan, V.B. Synthesis and characterization of new chitosan-based Schiff base compounds. Carbohydr. Polym.,  2016, 145, 37-47.
 [http://dx.doi.org/10.1016/j.carbpol.2016.02.076] [PMID: 27106149]

[6]
Yadav, P.; Sarkar, A.; Kumar, A. synthesis and biological activities of Schiff bases and their derivatives: A review of recent work. J. Basic. App. Eng. Res.,  2019, 6(1), 62-65.

[7]
Pervaiz, M.; Sadiq, S.; Sadiq, A.; Younas, U.; Ashraf, A.; Saeed, Z.; Zuber, M.; Adnan, A. Azo-Schiff base derivatives of transition metal complexes as antimicrobial agents. Coord. Chem. Rev.,  2021, 447, 214128.
 [http://dx.doi.org/10.1016/j.ccr.2021.214128]

[8]
Kate, S.S.; Thakare, N. Synthesis & spectral characterization of some Azo Amine Dyes. J. Global Biosci.,  2016, 5(1), 3615-3617.

[9]
Norhafiefa, H.; Yusoff, H.; Rahamathullah, R. Synthesis and characterization of alkoxy substituted p-cyano stilbene schiff bases IOP Conf. Ser.: Mater. Sci. Eng.,  2018, 440, 012016.
 [http://dx.doi.org/10.1088/1757-899X/440/1/012016]

[10]
Boceiri, N.; Benabdallah, T.; Hadj Youcef, M.; Reffas, H. Synthesis and characterization of a novel series of amphiphilic mercapto-1,2,4-triazole schiff base ligands: Investigation of their behavior in hydro-organic solutions. J. Surfactants Deterg.,  2016, 19(3), 583-597.
 [http://dx.doi.org/10.1007/s11743-016-1811-1]

[11]
Ibrahim, F.M. Polyether hexadentate schiff base ligand with trivalent chromium, iron, cobalt ions. J. Al-Nahrain. Univ. Sci.,  2017, 20(4), 1-6.

[12]
Bassanetti, I.; Atzeri, C.; Tinonin, D.A.; Marchiò, L. Silver(I) and thioether-bis(pyrazolyl)methane Ligands: The correlation between ligand functionalization and coordination polymer architecture. Cryst. Growth Des.,  2016, 16(6), 3543-3552.
 [http://dx.doi.org/10.1021/acs.cgd.6b00506]

[13]
Jaros, S.W.; Guedes da Silva, M.F.C.; Florek, M. Smoleński, P.; Pombeiro, A.J.L.; Kirillov, A.M. Silver(I) 1,3,5-Triaza-7-phosphaadamantane coordination polymers driven by substituted glutarate and malonate building blocks: Self-assembly synthesis, structural features, and antimicrobial properties. Inorg. Chem.,  2016, 55(12), 5886-5894.
 [http://dx.doi.org/10.1021/acs.inorgchem.6b00186] [PMID: 27244270]

[14]
Al Zoubi, W.; Al-Hamdani, A.A.S.; Ahmed, S.D.; Ko, Y.G. Synthesis, characterization, and biological activity of Schiff bases metal complexes. J. Phys. Org. Chem.,  2018, 31(2), e3752.
 [http://dx.doi.org/10.1002/poc.3752]

[15]
Dhokale, N.T.; Karale, B.K.; Nagawade, A.V. Synthesis, characterization and antibacterial studies on Mn (II) and Fe (II) complexes of N, O donor salicyloyl pyrazole oxime schiff bases. Orient. J. Chem.,  2017, 3(1), 165-172.
 [http://dx.doi.org/10.13005/ojc/330118]

[16]
Chai, L.Q.; Huang, J.J.; Zhang, J.Y.; Li, Y.X. Two 1-D and 2-D cobalt(II) complexes: Synthesis, crystal structures, spectroscopic and electrochemical properties. J. Coord. Chem.,  2015, 68(7), 1224-1237.
 [http://dx.doi.org/10.1080/00958972.2015.1019875]

[17]
Phenol, M. Kırca, B.K.; Tarı, G.Ö.; Kaştaş, Ç.A.; Odabaşoğlu, M. Crystal structure, spectral characterization, molecular modeling studies and structural effects of the proton transfer process for (E)- 5-methoxy-2-[(3,4-dimethylphenylimino) methyl] phenol. J. Chem. Chem. Eng.,  2017, 36(2), 265-278.

[18]
Sıdır, İ.; Sıdır, Y.G.; Berber, H.; Demiray, F. Emerging ground and excited state dipole moments and external electric field effect on electronic structure. A solvatochromism and theoretical study on 2- ((phenylimino)methyl)phenol derivatives. J. Mol. Liq.,  2015, 206, 56-67.
 [http://dx.doi.org/10.1016/j.molliq.2015.01.056]

[19]
Kazemi, Z.; Rudbari, H.A.; Sahihi, M.; Mirkhani, V.; Moghadam, M.; Tangestaninejad, S.; Mohammadpoor-Baltork, I.; Gharaghani, S. Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study. J. Photochem. Photobiol. B,  2016, 162, 448-462.
 [http://dx.doi.org/10.1016/j.jphotobiol.2016.07.003] [PMID: 27450299]

[20]
Messasma, Z.; Ourari, A.; Mahdadi, R.; Houchi, S.; Aggoun, D.; Kherbache, A.; Bentouhami, E. Synthesis, spectral characterization, DFT computational studies and inhibitory activity of novel N 2 S 2 tetradentates Schiff bases on metallo-beta-lactamases of Acinetobacter baumannii. J. Mol. Struct.,  2018, 1171, 672-681.
 [http://dx.doi.org/10.1016/j.molstruc.2018.06.044]

[21]
Abdel-Rahman, L.H.; Abu-Dief, A.M.; Adam, M.S.; Hamdan, S.K. Synthesis, spectral characterization and thermal behavior of newly derived La (III), Co (III) and Mn (II) Complexes with schiff base derived from methionine and salicylaldehyde. Catal. Lett.,  2016, 146, 1373-1396.
 [http://dx.doi.org/10.1007/s10562-016-1755-0]

[22]
Rochaa, M.; Ruizb, M.C.; Echeverríac, G.A.; Piroc, O.E.; Virgiliob, A.L.D.; Leónb, I.E.; Fronterae, A.; Gil, D.M. Diethyl-amino-phenyl-based Schiff base Cu (II) and V(IV) complexes: Experimental and theoretical study and cytotoxicity assays. New J. Chem.,  2013, 47, 1-12.

[23]
(a) Abdel-Rahman, L.H.; Adam, M.S.; Abu-Dief, A.M.; Moustafa, H.; Basha, M.; Aboria, A.H.; Al-Farhan, B.S.; Ahmed, H.E.S. Synthesis, theoretical investigations, biocidal screening, DNA binding, in vitro cytotoxicity and molecular docking of novel Cu (II), Pd (II) and Ag (I) complexes of chloro-benzylidene Schiff base: Promising antibiotic and anticancer agents. Appl. Organomet. Chem.,  2019, 32(12), e4527.
 [http://dx.doi.org/10.1002/aoc.4699]; 
(b) B. Rahman, L.H.A.; Dief, A.M.A.; Shehata, M.R.; Atlam, F.M.; Mawgoud, A.A.H.A. Some new Ag(I), VO(II) and Pd(II) chelates incorporating tridentate imine ligand: Design, synthesis, structure elucidation, density functional theory calculations for DNA interaction, antimicrobial and anticancer activities and molecular docking studies. Appl. Organomet. Chem.,  2019, 33(4), e4699.
 [http://dx.doi.org/10.1002/aoc.4699]

[24]
Dief, A.M.A.; Rahman, L.H.A.; Hassan, A.A.; Mawgoud, A. A robust in vitro anticancer, antioxidant and antimicrobial agents based on new metal-azomethine chelates incorporating Ag (I), Pd (II) and VO (II) cations: Probing the aspects of DNA interaction. Appl. Organomet. Chem.,  2020, 34(2), e5373.

[25]
Kostova, I.; Saso, L. Advances in research of Schiff-base metal complexes as potent antioxidants. Curr. Med. Chem.,  2013, 20(36), 4609-4632.
 [http://dx.doi.org/10.2174/09298673113209990149] [PMID: 23834186]

[26]
Agrawal, S. Drug -metal complexes in research - A review. Ultra-Scientist,  2015, 27(2), 113-116.

[27]
Kareem, I.; Hadi, M. Synthesis and characterization of some transition metal complexes with new azo- schiff base ligand 3,4-bis(((1E,2E)-2-((2-((4-((Z)-(3-Hydroxyphenyl)Diazenyl)Naphthalen-1-yl)amino)ethyl) imino)-1,2-Diphenylethylidene) Amino)Phenyl)(phenyl)Methanone. Egypt. J. Chem.,  2020, 63(1), 301-313.
 [http://dx.doi.org/10.21608/ejchem.2019.18924.2166]

[28]
Modi, J.A.; Desai, K.R.; Lokhandwala, S.R. Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities. Eur. J. Med. Chem.,  2014, 3(3), 1875-1885.

[29]
Shorouk, S.; Mukhtar, H.A.S.; Morsy, N.M.; Hafez, T.S.; Hassaneen, H.M.; Saleh, F.M. Overview on synthesis, reactions, applications, and biological activities of schiff bases. Egypt. J. Chem.,  2021, 64(11), 6541-6554.

[30]
Ghanghas, P.; Choudhary, A.; Kumar, D.; Poonia, K. Coordination metal complexes with Schiff bases: Useful pharmacophores with comprehensive biological applications. Inorg. Chem. Commun.,  2021, 130, 108710.
 [http://dx.doi.org/10.1016/j.inoche.2021.108710]

[31]
Ghosh, P.; Dey, S.; Ara, M.; Karim, K.; Islam, A.B.M.N. A review on synthesis and versatile applications of some selected Schiff bases with their transition metal complexes. Egypt. J. Chem.,  2019, 63(Part 2), 523-547.
 [http://dx.doi.org/10.21608/ejchem.2019.13741.1852]

[32]
Xavier, D.A.; Srividhya, N. Synthesis and study of schiff base ligands. IOSR J. App. Chem.,  2014, 7(11), 06-15.
 [http://dx.doi.org/10.9790/5736-071110615]

[33]
Sinha, D.; Tiwari, A.K.; Singh, S.; Shukla, G. Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde. Eur. J. Med. Chem.,  2008, 43(1), 160-165.
 [http://dx.doi.org/10.1016/j.ejmech.2007.03.022] [PMID: 17532543]

[34]
Karthikeyan, M.S.; Parsad, D.J.; Poojary, B.; Bhat, K.S.; Holla, B.S.; Kumari, N.S. Synthesis and biological activity of Schiff and mannich bases bearing 2,4-dichloro-5-fluorophenyl moiety. Bioorg. Med. Chem.,  2006, 14(22), 7482-7489.
 [http://dx.doi.org/10.1016/j.bmc.2006.07.015] [PMID: 16879972]

[35]
Singh, K.; Barwa, M.; Tyagi, P. Synthesis, characterization and biological studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with bidentate Schiff bases derived by heterocyclic ketone. Eur. J. Med. Chem.,  2006, 41(1), 147-153.
 [http://dx.doi.org/10.1016/j.ejmech.2005.06.006] [PMID: 16271421]

[36]
Panneerselvam, P.; Nair, R.R.; Vijayalakshmi, G.; Subramanian, E.H.; Sridhar, S.K. Synthesis of Schiff bases of 4-(4-aminophenyl)-morpholine as potential antimicrobial agents. Eur. J. Med. Chem.,  2005, 40(2), 225-229.
 [http://dx.doi.org/10.1016/j.ejmech.2004.09.003] [PMID: 15694658]

[37]
Sridhar, S.K.; Saravanan, M.; Ramesh, A. Synthesis and antibacterial screening of hydrazones, Schiff and Mannich bases of isatin derivatives. Eur. J. Med. Chem.,  2001, 36(7-8), 615-625.
 [http://dx.doi.org/10.1016/S0223-5234(01)01255-7] [PMID: 11600231]

[38]
Wang, X.; Ding, G.; Duan, Y.; Zhu, Y.; Zhu, G.; Wang, M.; Li, X.; Zhang, Y.; Qin, X.; Hung, C.H. A novel triphenylamine-based bis-Schiff bases fluorophores with AIE-Activity as the hydrazine fluorescence turn-off probes and cell imaging in live cells. Talanta,  2020, 217, 121029.
 [http://dx.doi.org/10.1016/j.talanta.2020.121029] [PMID: 32498835]

[39]
Ceramella, J.; Iacopetta, D.; Catalano, A.; Cirillo, F.; Lappano, R.; Sinicropi, M.S. A review on the antimicrobial activity of schiff bases: Data collection and recent studies. Antibiotics,  2022, 11(2), 191.
 [http://dx.doi.org/10.3390/antibiotics11020191] [PMID: 35203793]

[40]
Ronconi, L.; Sigel, A.; Sigel, H.; Freisinger, E.; Sigel, R.K.O. Metallo-drugs: Development and action of anticancer agents. Transition Met. Chem.,  2018, 43(5), 377-379.

[41]
Murray, B.S.; Dyson, P.J. Recent progress in the development of organometallics for the treatment of cancer. Curr. Opin. Chem. Biol.,  2020, 56, 28-34.
 [http://dx.doi.org/10.1016/j.cbpa.2019.11.001] [PMID: 31812831]

[42]
Spinello, A.; Magistrato, A. An omics perspective to the molecular mechanisms of anticancer metallo-drugs in the computational microscope era. Expert Opin. Drug Discov.,  2017, 12(8), 1-13.
 [http://dx.doi.org/10.1080/17460441.2017.1340272] [PMID: 28604114]

[43]
Chow, M.J.; Babak, M.V.; Wong, D.Y.Q.; Pastorin, G.; Gaiddon, C.; Ang, W.H. Structural determinants of p53-independence in anticancer ruthenium-arene Schif-base complexes. Mol. Pharm.,  2016, 13(7), 2543-2554.
 [http://dx.doi.org/10.1021/acs.molpharmaceut.6b00348] [PMID: 27174050]

[44]
Hussain, A.; AlAjmi, M.F.; Rehman, M.T.; Amir, S.; Husain, F.M.; Alsalme, A.; Siddiqui, M.A.; AlKhedhairy, A.A.; Khan, R.A. Copper(II) complexes as potential anticancer and Nonsteroidal anti-inflammatory agents: In vitro and in vivo studies. Sci. Rep.,  2019, 9(1), 5237.
 [http://dx.doi.org/10.1038/s41598-019-41063-x] [PMID: 30918270]

[45]
Zhang, P.; Sadler, P.J. Advances in the design of organometallic anticancer complexes. J. Organomet. Chem.,  2017, 839, 5-14.
 [http://dx.doi.org/10.1016/j.jorganchem.2017.03.038]

[46]
More, M.S.; Joshi, P.G.; Mishra, Y.K.; Khanna, P.K. Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: A review. Mater. Today Chem.,  2019, 14, 100195.
 [http://dx.doi.org/10.1016/j.mtchem.2019.100195] [PMID: 32289101]

[47]
Liu, X.; Hamon, J-R. Recent developments in penta-, hexa- and heptadentate Schiff base ligands and their metal complexes. Coord. Chem. Rev.,  2019, 389, 94-118.
 [http://dx.doi.org/10.1016/j.ccr.2019.03.010]

[48]
Shekhar, S.; Khan, A.M.; Sharma, S.; Sharma, B.; Sarkar, A. Schiff base metallodrugs in antimicrobial and anticancer chemotherapy applications: A comprehensive review. Emergent Mater.,  2021, 5, 279-293.
 [http://dx.doi.org/10.1007/s42247-021-00234-1]

[49]
Simpson, D.H.; Scott, P. Antimicrobial metallodrugs. In: Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells; Academic Press: Cambridge, Massachusetts, 2017, pp. 205-243.

[50]
Thompson, K.H.; McNeill, J.H.; Orvig, C. Vanadium compounds as insulin mimics. Chem. Rev.,  1999, 99(9), 2561-2572.
 [http://dx.doi.org/10.1021/cr980427c] [PMID: 11749492]

[51]
Grivani, G.; Bruno, G.; Rudbari, H.A.; Khalaji, A.D.; Pourteimouri, P. Synthesis, characterization and crystal structure determination of a new oxovanadium(IV) Schiff base complex: The catalytic activity in the epoxidation of cyclooctene. Inorg. Chem. Commun.,  2012, 18, 15-20.
 [http://dx.doi.org/10.1016/j.inoche.2011.12.044]

[52]
Pyrz, J.W.; Roe, A.L.; Stern, L.J.; Que, L., Jr Model studies of iron-tyrosinate proteins. J. Am. Chem. Soc.,  1985, 107(3), 614-620.
 [http://dx.doi.org/10.1021/ja00289a013]

[53]
Tümer, M.; Erdogan, B.; Köksal, H.; Serin, S.; Nutku, M.Y. Preparation, spectroscopic characterisation and thermal analyses studies of the Cu(II), Pd(II) and VO(IV) complexes of some Schiff base ligands. Synth. React. Inorg. Met.-Org. Chem.,  1998, 28(4), 529-542.
 [http://dx.doi.org/10.1080/00945719809351663]

[54]
Ejidike, I.P.; Ajibade, P.A. Synthesis, characterization, anticancer, and antioxidant studies of Ru(III) complexes of monobasic tridentate schiff bases. Bioinorg. Chem. Appl.,  2016, 2016, 1-11.
 [http://dx.doi.org/10.1155/2016/9672451] [PMID: 27597814]

[55]
Calderon, A.; Teles, R.; Leite, J.R.; Bloch, J., Jr; Astolfi-Filho, S.; Freitas, M. Serine protease inhibitors from Amazon leguminosae seeds: Purification and preliminary characterization of two chymotrypsin inhibitors from Inga umbratica. Protein Pept. Lett.,  2001, 8(6), 485-493.
 [http://dx.doi.org/10.2174/0929866013409175]

[56]
Cozzi, P.G. Metal–Salen Schiff base complexes in catalysis: Practical aspects. Chem. Soc. Rev.,  2004, 33(7), 410-421.
 [http://dx.doi.org/10.1039/B307853C] [PMID: 15354222]

[57]
Katsuki, T. Unique asymmetric catalysis of cis-? metal complexes of salen and its related Schiff-base ligands. Chem. Soc. Rev.,  2004, 33(7), 437-444.
 [http://dx.doi.org/10.1039/b304133f] [PMID: 15354225]

[58]
Fakhr, I.M.I.; Hamdy, N.A.; Radwan, M.A.; Ahmed, Y.M. Synthesis of new bioactive benzothiophene derivatives. Egypt. J. Chem.,  2004, 47, 201-215.

[59]
Ammar, R.A.A.; Alaghaz, A.N.M.A. Synthesis, spectroscopic characterization and potentiometric studies of a tetradentate [N2O2] schiff base, N,N -bis(2-hydroxybenzylidene)-1,1-diaminoethane and its Co(II),Ni(II),Cu(II) and Zn(II) complexes. Int. J. Electrochem. Sci.,  2013, 8(6), 8686-8699.

[60]
Gaballa, A.S.; Asker, M.S.; Barakat, A.S.; Teleb, S.M. Synthesis, characterization and biological activity of some platinum(II) complexes with Schiff bases derived from salicylaldehyde, 2-furaldehyde and phenylenediamine. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2007, 67(1), 114-121.
 [http://dx.doi.org/10.1016/j.saa.2006.06.031] [PMID: 16942911]

[61]
Dilruba, S.; Kalayda, G.V. Platinum-based drugs: Past, present and future. Cancer Chemother. Pharmacol.,  2016, 77(6), 1103-1124.
 [http://dx.doi.org/10.1007/s00280-016-2976-z] [PMID: 26886018]

[62]
Giaccone, G.; Herbst, R.S.; Manegold, C.; Scagliotti, G.V.; Rosell, R.; Miller, V.; Natale, R.B.; Schiller, J.H.; Von Pawel, J.; Pluzanska, A.; Gatzemeier, U. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial--INTACT 1. J. Clin. Oncol.,  2004, 22(5), 777-784.

[63]
Zeng, L.; Chen, Y.; Liu, J.; Huang, H.; Guan, R.; Ji, L.; Chao, H. Ruthenium (II) complexes with 2-phenylimidazo [4, 5-f][1, 10] phenanthroline derivatives that strongly combat cisplatin-resistant tumor cells. Sci. Rep.,  2016, 6(1), 19449.
 [http://dx.doi.org/10.1038/srep19449] [PMID: 26763798]

[64]
Wang, F.X.; Chen, M.H.; Hu, X.Y.; Ye, R.R.; Tan, C.P.; Ji, L.N.; Mao, Z.W. Ester-modified cyclometalated iridium (III) complexes as mitochondria-targeting anticancer agents. Sci. Rep.,  2016, 6(1), 38954.
 [http://dx.doi.org/10.1038/srep38954] [PMID: 27958338]

[65]
Khan, R.A.; Usman, M.; Dhivya, R.; Balaji, P.; Alsalme, A.; AlLohedan, H.; Arjmand, F.; AlFarhan, K.; Akbarsha, M.A.; Marchetti, F.; Pettinari, C.; Tabassum, S. Heteroleptic copper (I) complexes of “scorpionate” bis-pyrazolyl carboxylate ligand with auxiliary phosphine as potential anticancer agents: An insight into cytotoxic mode. Sci. Rep.,  2017, 7(1), 45229.
 [http://dx.doi.org/10.1038/srep45229] [PMID: 28338061]

[66]
Qin, J.L.; Shen, W.Y.; Chen, Z.F.; Zhao, L.F.; Qin, Q.P.; Yu, Y.C.; Liang, H. Oxoaporphine metal complexes (CoII, NiII, ZnII) with high antitumor activity by inducing mitochondria-mediated apoptosis and S-phase arrest in HepG2. Sci. Rep.,  2017, 7(1), 46056.
 [http://dx.doi.org/10.1038/srep46056] [PMID: 28436418]

[67]
Schwartz, J.A.; Lium, E.K.; Silverstein, S.J. Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC-96. J. Virol.,  2001, 75(9), 4117-4128.
 [http://dx.doi.org/10.1128/JVI.75.9.4117-4128.2001] [PMID: 11287561]

[68]
Munteanu, C.R.; Suntharalingam, K. Advances in cobalt complexes as anticancer agents. Dalton Trans.,  2015, 44(31), 13796-13808.
 [http://dx.doi.org/10.1039/C5DT02101D] [PMID: 26148776]

[69]
Glasner, H.; Tshuva, E.Y. A marked synergistic effect in antitumor activity of salan titanium(IV) complexes bearing two differently substituted aromatic rings. J. Am. Chem. Soc.,  2011, 133(42), 16812-16814.
 [http://dx.doi.org/10.1021/ja208219f] [PMID: 21967133]

[70]
Glasner, H.; Tshuva, E.Y. C1-symmetrical titanium(IV) complexes of salan ligands with differently substituted aromatic rings: Enhanced cytotoxic activity. Inorg. Chem.,  2014, 53(6), 3170-3176.
 [http://dx.doi.org/10.1021/ic500001j] [PMID: 24588655]

[71]
King, A.P.; Gellineau, H.A.; Ahn, J.E.; MacMillan, S.N.; Wilson, J.J. Bis(thiosemicarbazone) Complexes of Cobalt(III). Synthesis, Characterization, and Anticancer Potential. Inorg. Chem.,  2017, 56(11), 6609-6623.
 [http://dx.doi.org/10.1021/acs.inorgchem.7b00710] [PMID: 28509538]

[72]
Ibrahim, F.M.; Abdalhadi, S.M. Performance of schiff bases metal complexes and their ligand in biological activity: A review, al-nahrain. J. Sci.,  2021, 24(1), 1-10.
 [http://dx.doi.org/10.22401/ANJS.24.1.01]

[73]
Duff, B.; Reddy Thangella, V.; Creaven, B.S.; Walsh, M.; Egan, D.A. Anti-cancer activity and mutagenic potential of novel copper(II) quinolinone Schiff base complexes in hepatocarcinoma cells. Eur. J. Pharmacol.,  2012, 689(1-3), 45-55.
 [http://dx.doi.org/10.1016/j.ejphar.2012.06.004] [PMID: 22705894]

[74]
Raja, G.; Butcher, R.J.; Jayabalakrishnan, C. Synthesis, characterization, DNA binding and cleavage properties and anticancer studies of ruthenium(III) Schiff base complexes. Trans. Met. Chem.,  2012, 37(2), 169-174.
 [http://dx.doi.org/10.1007/s11243-011-9571-2]

[75]
Sathiyaraj, S.; Butcher, R.J.; Jayabalakrishnan, C. Synthesis, characterization, DNA interaction and in vitro cytotoxicity activities of ruthenium(II) Schiff base complexes. J. Mol. Struct.,  2012, 1030, 95-103.
 [http://dx.doi.org/10.1016/j.molstruc.2012.07.021]

[76]
Rosenberg, B.; Van Camp, L.; Krigas, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature,  1965, 205(4972), 698-699.
 [http://dx.doi.org/10.1038/205698a0] [PMID: 14287410]

[77]
Jakupec, M.A.; Galanski, M.S.; Arion, V.B.; Hartinger, C.G.; Keppler, B.K. Antitumour metal compounds: More than theme and variations. Dalton Trans.,  2007, 2(2), 183-194.
 [http://dx.doi.org/10.1039/B712656P] [PMID: 18097483]

[78]
Clarke, M.J.; Bitler, S.; Rennert, D.; Buchbinder, M.; Kelman, A.D. Reduction and subsequent binding of ruthenium ions catalyzed by subcellular components. J. Inorg. Biochem.,  1980, 12(1), 79-87.
 [http://dx.doi.org/10.1016/S0162-0134(00)80045-8] [PMID: 7373292]

[79]
Dyson, P.J.; Sava, G. Metal-based antitumour drugs in the post genomic era. Dalton Trans.,  2006, 16(16), 1929-1933.
 [http://dx.doi.org/10.1039/b601840h] [PMID: 16609762]

[80]
Dale, L.D.; Tocher, J.H.; Dyson, T.M.; Edwards, D.I.; Tocher, D.A. Studies on DNA damage and induction of SOS repair by novel multifunctional bioreducible compounds. II. A metronidazole adduct of a ruthenium-arene compound. Anticancer Drug Des.,  1992, 7(1), 3-14.
 [PMID: 1543526]

[81]
Yan, Y.K.; Melchart, M.; Habtemariam, A.; Sadler, P.J. Organometallic chemistry, biology and medicine: Ruthenium arene anticancer complexes. Chem. Commun.,  2005, 38(38), 4764-4776.
 [http://dx.doi.org/10.1039/b508531b] [PMID: 16193110]

[82]
Azam, M.; Warad, I.; Al-Resayes, S.; Shakir, M.; Ullah, M.F.; Ahmad, A.; Sarkar, F.H. A novel Ru(II) complex derived from hydroxydiamine as a potential antitumor agent: Synthesis and Structural Characterization. Inorg. Chem. Commun.,  2012, 20, 252-258.
 [http://dx.doi.org/10.1016/j.inoche.2012.03.019]

[83]
Proetto, M.; Liu, W.; Hagenbach, A.; Abram, U.; Gust, R. Synthesis, characterization and in vitro antitumour activity of a series of novel platinum(II) complexes bearing Schiff base ligands. Eur. J. Med. Chem.,  2012, 53, 168-175.
 [http://dx.doi.org/10.1016/j.ejmech.2012.03.053] [PMID: 22534185]

[84]
Obeid, A.; El-Shekeil, A.; Al-Aghbari, S.; Al-Shabi, J. Anticancer, DNA cleavage, and antimicrobial activity studies of some new Schiff-base titanium(IV) complexes. J. Coord. Chem.,  2012, 65(15), 2762-2770.
 [http://dx.doi.org/10.1080/00958972.2012.703780]

[85]
Raja, G.; Butcher, R.J.; Jayabalakrishnan, C. Studies on synthesis, characterization, DNA interaction and cytotoxicity of ruthenium(II) Schiff base complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2012, 94, 210-215.
 [http://dx.doi.org/10.1016/j.saa.2012.03.035] [PMID: 22522297]

[86]
Zhang, N.; Fan, Y.; Zhang, Z.; Zuo, J.; Zhang, P.; Wang, Q.; Liu, S.; Bi, C. Syntheses, crystal structures and anticancer activities of three novel transition metal complexes with Schiff base derived from 2-acetylpyridine and l-tryptophan. Inorg. Chem. Commun.,  2012, 22, 68-72.
 [http://dx.doi.org/10.1016/j.inoche.2012.05.022]

[87]
Ghorab, M.M.; Shaaban, M.A.; Refaat, H.M.; Heiba, H.I.; Ibrahim, S.S. Anticancer and radiosensitizing evaluation of some new pyranothiazole-Schiff bases bearing the biologically active sulfonamide moiety. Eur. J. Med. Chem.,  2012, 53, 403-407.
 [http://dx.doi.org/10.1016/j.ejmech.2012.04.009] [PMID: 22583778]

[88]
Li, X.; Li, X.Q.; Liu, H.M.; Zhou, X.Z.; Shao, Z.H. Synthesis and evaluation of antitumor activities of novel chiral 1,2,4-triazole Schiff bases bearing γ-butenolide moiety. Org. Med. Chem. Lett.,  2012, 2(1), 26.
 [http://dx.doi.org/10.1186/2191-2858-2-26] [PMID: 22759342]

[89]
Amer, S.; El-Wakiel, N.; El-Ghamry, H. Synthesis, spectral, antitumor and antimicrobial studies on Cu(II) complexes of purine and triazole Schiff base derivatives. J. Mol. Struct.,  2013, 1049, 326-335.
 [http://dx.doi.org/10.1016/j.molstruc.2013.06.059]

[90]
Ali, I.; Haque, A.; Saleem, K.; Hsieh, M.F. Curcumin-I Knoevenagel’s condensates and their Schiff’s bases as anticancer agents: Synthesis, pharmacological and simulation studies. Bioorg. Med. Chem.,  2013, 21(13), 3808-3820.
 [http://dx.doi.org/10.1016/j.bmc.2013.04.018] [PMID: 23643901]

[91]
Chaviara, A.T.; Christidis, P.C.; Papageorgiou, A.; Chrysogelou, E.; Hadjipavlou-Litina, D.J.; Bolos, C.A. In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H2O). J. Inorg. Biochem.,  2005, 99(11), 2102-2109.
 [http://dx.doi.org/10.1016/j.jinorgbio.2005.07.011] [PMID: 16144711]

[92]
Nagane, R.; Chikira, M.; Oumi, M.; Shindo, H.; Antholine, W.E. How amino acids control the binding of Cu(II) ions to DNA. J. Inorg. Biochem.,  2000, 78(3), 243-249.
 [http://dx.doi.org/10.1016/S0162-0134(00)00019-2] [PMID: 10805181]

[93]
Singh, N.K.; Singh, S.B. Antitumour and immunomodulatory effects of Cu(lI) complexes of thiobenzyhdrazide. Met. Based Drugs,  2002, 9, 109-118.
 [http://dx.doi.org/10.1155/MBD.2002.109] [PMID: 18475431]

[94]
Zhang, H.; Joseph, J.; Gurney, M.; Becker, D.; Kalyanaraman, B. Bicarbonate enhances peroxidase activity of Cu,Zn-superoxide dismutase. Role of carbonate anion radical and scavenging of carbonate anion radical by metalloporphyrin antioxidant enzyme mimetics. J. Biol. Chem.,  2002, 277(2), 1013-1020.
 [http://dx.doi.org/10.1074/jbc.M108585200] [PMID: 11682485]

[95]
Barve, A.; Kumbhar, A.; Bhat, M.; Joshi, B.; Butcher, R.; Sonawane, U.; Joshi, R. Mixed-ligand copper(II) maltolate complexes: Synthesis, characterization, DNA binding and cleavage, and cytotoxicity. Inorg. Chem.,  2009, 48(19), 9120-9132.
 [http://dx.doi.org/10.1021/ic9004642] [PMID: 19780613]

[96]
Rajendiran, V.; Karthik, R.; Palaniandavar, M.; Stoeckli-Evans, H.; Periasamy, V.S.; Akbarsha, M.A.; Srinag, B.S.; Krishnamurthy, H. Mixed-ligand copper(II)-phenolate complexes: Effect of coligand on enhanced DNA and protein binding, DNA cleavage, and anticancer activity. Inorg. Chem.,  2007, 46(20), 8208-8221.
 [http://dx.doi.org/10.1021/ic700755p] [PMID: 17784750]

[97]
Sathiyaraj, S.; Sampath, K.; Butcher, R.J.; Pallepogu, R.; Jayabalakrishnan, C. Designing, structural elucidation, comparison of DNA binding, cleavage, radical scavenging activity and anticancer activity of copper(I) complex with 5-dimethyl-2-phenyl-4-[(pyridin-2-ylmethylene)-amino]-1,2-dihydro-pyrazol-3-one Schiff base ligand. Eur. J. Med. Chem.,  2013, 64, 81-89.
 [http://dx.doi.org/10.1016/j.ejmech.2013.03.047] [PMID: 23644191]

[98]
Shukla, S.; Srivastava, R.S.; Shrivastava, S.K.; Sodhi, A.; Kumar, P. Synthesis, characterization, in vitro anticancer activity, and docking of Schiff bases of 4-amino-1,2-naphthoquinone. Med. Chem. Res.,  2013, 22(4), 1604-1617.
 [http://dx.doi.org/10.1007/s00044-012-0150-7]

[99]
Li, L.J.; Wang, C.; Tian, C.; Yang, X.Y.; Hua, X.X.; Du, J.L. Water-soluble platinum(II) complexes of reduced amino acid Schiff bases: Synthesis, characterization, and antitumor activity. Res. Chem. Intermed.,  2013, 39(2), 733-746.
 [http://dx.doi.org/10.1007/s11164-012-0593-y]

[100]
Noureen, A.; Saleem, S.; Fatima, T.; Siddiqi, H.M.; Mirza, B. Synthesis, characterization, biological evaluation and QSAR of some Schiff base esters: Promising new antitumor, antioxidant and anti-inflammatory agents. Pak. J. Pharm. Sci.,  2013, 26(1), 113-123.
 [PMID: 23261736]

[101]
Aazam, E.S.; El-Said, W.A. Synthesis of copper/nickel nanoparticles using newly synthesized Schiff-base metals complexes and their cytotoxicity/catalytic activities. Bioorg. Chem.,  2014, 57, 5-12.
 [http://dx.doi.org/10.1016/j.bioorg.2014.07.004] [PMID: 25159596]

[102]
Selwin Joseyphus, R.; Shiju, C.; Joseph, J.; Justin Dhanaraj, C.; Arish, D. Synthesis and characterization of metal complexes of Schiff base ligand derived from imidazole-2-carboxaldehyde and 4-aminoantipyrine. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2014, 133, 149-155.
 [http://dx.doi.org/10.1016/j.saa.2014.05.050] [PMID: 24934973]

[103]
Chandra, S. Vandana, Synthesis, spectroscopic, anticancer and antibacterial studies of Ni(II) and Cu(II) complexes with 2-carboxybenzaldehyde thiosemicarbazone. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2014, 129, 333-338.
 [http://dx.doi.org/10.1016/j.saa.2014.02.141] [PMID: 24747857]

[104]
Ghosh, S.; Misra, A.K.; Bhatia, G.; Khan, M.M.; Khanna, A.K. Syntheses and evaluation of glucosyl aryl thiosemicarbazide and glucosyl thiosemicarbazone derivatives as antioxidant and anti-dyslipidemic agents. Bioorg. Med. Chem. Lett.,  2009, 19(2), 386-389.
 [http://dx.doi.org/10.1016/j.bmcl.2008.11.070] [PMID: 19064319]

[105]
Lobana, T.S.; Rekha, B.S.; Sidhu, B.S.; Castineiras, A.; Bermejo, E.; Nishioka, T. Syntheses, NMR (1H, 31P) spectroscopy and crystal structures of complexes of copper(I) halides with isatin-3-thiosemicarbazones. J. Coord. Chem.,  2005, 58(9), 803-809.
 [http://dx.doi.org/10.1080/00958970500110974]

[106]
Tripathi, L.; Kumar, P.; Singhai, A.K. Role of chelates in treatment of cancer. Indian J. Cancer,  2007, 44(2), 62-71.
 [http://dx.doi.org/10.4103/0019-509X.35813] [PMID: 17938483]

[107]
Tripathi, K.A. Review – Can metal ions be incorporated into drugs? Asian J. Res. Chem,  2009, 2(1), 14.

[108]
Cerchiaro, G.; Aquilano, K.; Filomeni, G.; Rotilio, G.; Ciriolo, M.R.; Ferreira, A.M.D.C. Isatin-Schiff base copper(II) complexes and their influence on cellular viability. J. Inorg. Biochem.,  2005, 99(7), 1433-1440.
 [http://dx.doi.org/10.1016/j.jinorgbio.2005.03.013] [PMID: 15878622]

[109]
Hancock, C.N.; Stockwin, L.H.; Han, B.; Divelbiss, R.D.; Jun, J.H.; Malhotra, S.V.; Hollingshead, M.G.; Newton, D.L. A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic. Biol. Med.,  2011, 50(1), 110-121.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.696] [PMID: 20971185]

[110]
Cristina, M. Copper complexes as anticancer agents. Anticancer Agents Med. Chem.,  2009, 9(2), 185-211.
 [http://dx.doi.org/10.2174/187152009787313837] [PMID: 19199864]

[111]
Sathisha, M.P.; Revankar, V.K.; Pai, K.S.R. Synthesis, structure, electrochemistry, and spectral characterization of bis-isatin thiocarbohydrazone metal complexes and their antitumor activity against ehrlich ascites carcinoma in swiss albino mice. Met. Based Drugs,  2008, 2008, 1-11.
 [http://dx.doi.org/10.1155/2008/362105] [PMID: 18320020]

[112]
Lobana, T.S. Rekha; Pannu, A.P.S.; Hundal, G.; Butcher, R.J.; Castineiras, A. Synthesis and structures of monomeric [chloro(isatin-3-thiosemicarbazone)bis(triphenylphosphine)]copper(I) and dimeric [dichlorobis(thiophene-2-carbaldehyde thiosemicarbazone)bis(triphenylphosphine)]dicopper(I)] complexes. Polyhedron,  2007, 26(12), 2621-2628.
 [http://dx.doi.org/10.1016/j.poly.2006.12.044]

[113]
Ali, A.Q.; Teoh, S.G.; Eltayeb, N.E.; Khadeer Ahamed, M.B.; Abdul Majid, A.M.S. Synthesis of copper(II) complexes of isatin thiosemicarbazone derivatives: In vitro anti-cancer, DNA binding, and cleavage activities. Polyhedron,  2014, 74, 6-15.
 [http://dx.doi.org/10.1016/j.poly.2014.02.025]

[114]
El-Sonbati, A.Z.; Diab, M.A.; El-Bindary, A.A.; Abd El-Kader, M.K. Supramolecular and structural modification on conformational by mixed ligand. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2012, 99, 211-217.
 [http://dx.doi.org/10.1016/j.saa.2012.09.016] [PMID: 23064551]

[115]
Shiju, C.; Arish, D.; Bhuvanesh, N.; Kumaresan, S. Synthesis, characterization, and biological evaluation of Schiff base–platinum(II) complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2015, 145, 213-222.
 [http://dx.doi.org/10.1016/j.saa.2015.02.030] [PMID: 25782179]

[116]
Mahmoud, W.H.; Deghadi, R.G.; Mohamed, G.G. Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity. Appl. Organomet. Chem.,  2016, 30(4), 221-230.
 [http://dx.doi.org/10.1002/aoc.3420]

[117]
Abd-Elzaher, M.M.; Labib, A.A.; Mousa, H.A.; Moustafa, S.A.; Ali, M.M.; El-Rashedy, A.A. Synthesis, anticancer activity and molecular docking study of Schiff base complexes containing thiazole moiety. Beni. Suef Univ. J. Basic Appl. Sci.,  2016, 5(1), 85-96.
 [http://dx.doi.org/10.1016/j.bjbas.2016.01.001]

[118]
Ejidike, I.; Ajibade, P. Ruthenium(III) complexes of heterocyclic tridentate (ONN) schiff base: Synthesis, characterization and its biological properties as an antiradical and antiproliferative agent. Int. J. Mol. Sci.,  2016, 17(1), 60.
 [http://dx.doi.org/10.3390/ijms17010060] [PMID: 26742030]

[119]
Kamatchi, T.S.; Chitrapriya, N.; Lee, H.; Fronczek, C.F.; Fronczek, F.R.; Natarajan, K. Ruthenium(II)/(III) complexes of 4-hydroxy-pyridine-2,6-dicarboxylic acid with PPh3/AsPh3 as co-ligand: Impact of oxidation state and co-ligands on anticancer activity in vitro. Dalton Trans.,  2012, 41(7), 2066-2077.
 [http://dx.doi.org/10.1039/C1DT11273B] [PMID: 22183160]

[120]
Kirubavathy, S.J.; Saranya, J.; Sathya, N.; Enoch, I.V.M.V.; Selvakumar, P.M.; Chitra, S. Synthesis, characterization and biological evaluation of Ru(III) mercaptopyrimidine Schiff base complexes. Appl. Organomet. Chem.,  2017, 31(11), e3760.
 [http://dx.doi.org/10.1002/aoc.3760]

[121]
El-Halim, H. F. A.; Mohamed, G. G.; Anwar, M. N. Antimicrobial and anticancer activities of Schiff base ligand and its transition metal mixed ligand complexes with heterocyclic base. Appl. Organomet. Chem.,  2017, 31(1), e3899.
 [http://dx.doi.org/10.1002/aoc.3899]

[122]
Gou, Y.; Li, J.; Fan, B.; Xu, B.; Zhou, M.; Yang, F. Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes as potential anticancer agents. Eur. J. Med. Chem.,  2017, 134, 207-217.
 [http://dx.doi.org/10.1016/j.ejmech.2017.04.026] [PMID: 28415010]

[123]
Kuamr, K.S.; Varma, C.P.; Reena, V.N.; Aravindakshan, K.K. Synthesis, characterization, cytotoxic, anticancer and antimicrobial studies of novel schiff base ligand derived from vanillin and its transition metal complexes. Pharm. Sci. Res.,  2017, 9(8), 1317-1323.

[124]
Magd-El-Din, A.A.; Mousa, H.A.; Labib, A.A.; Hassan, A.S.; Abd El-All, A.S.; Ali, M.M.; El-Rashedy, A.A.; El-Desoky, A.H. Benzimidazole – Schiff bases and their complexes: Synthesis, anticancer activity and molecular modeling as Aurora kinase inhibitor. Z. Naturforsch. C J. Biosci.,  2018, 73(11-12), 465-478.
 [http://dx.doi.org/10.1515/znc-2018-0010] [PMID: 30205654]

[125]
Mahmoud, W.H.; Omar, M.M.; Sayed, F.N.; Mohamed, G.G. Synthesis, characterization, spectroscopic and theoretical studies of transition metal complexes of new nano Schiff base derived from L-histidine and 2-acetylferrocene and evaluation of biological and anticancer activities. Appl. Organomet. Chem.,  2018, 32(7), e4386.
 [http://dx.doi.org/10.1002/aoc.4386]

[126]
Sukanya, P.; Reddy, C.V.R. Synthesis, characterization and in vitro anticancer, DNA binding and cleavage studies of Mn (II), Co (II), Ni (II) and Cu (II) complexes of Schiff base ligand 3-(2-(1-(1H- benzimidazol-2-yl)ethylidene)hydrazinyl)quinoxalin-2(1H)- one and crystal structure of the ligand. Appl. Organomet. Chem.,  2018, 32(11), e4526.

[127]
Devi, J.; Yadav, M.; Kumar, D.; Naik, L.S.; Jindal, D.K. Some divalentmetal(II) complexes of salicylaldehyde-derived Schiff bases: Synthesis, spectroscopic characterization, antimicrobial and in vitro anticancer studies. Appl. Organomet. Chem.,  2018, 33(2), e4693.

[128]
Narvi, E.; Jaakkola, K.; Winsel, S.; Oetken-Lindholm, C.; Halonen, P.; Kallio, L.; Kallio, M.J. Altered TUBB3 expression contributes to the epothilone response of mitotic cells. Br. J. Cancer,  2013, 108(1), 82-90.
 [http://dx.doi.org/10.1038/bjc.2012.553] [PMID: 23321512]

[129]
Balakrishnan, C.; Theetharappan, M.; Kowsalya, P.; Natarajan, S.; Neelakantan, M.A.; Mariappan, S.S. Biocatalysis, DNA–protein interactions, cytotoxicity and molecular docking of Cu(II), Ni(II), Zn(II) and V(IV) Schiff base complexes. Appl. Organomet. Chem.,  2017, 31(11), e3776.
 [http://dx.doi.org/10.1002/aoc.3776]

[130]
Mishra, V.R.; Ghanavatkar, C.W.; Mali, S.N.; Chaudhari, H.K.; Sekar, N. Schiff base clubbed benzothiazole: Synthesis, potent antimicrobial and MCF-7 anticancer activity, DNA cleavage and computational study. J. Biomol. Struct. Dyn.,  2020, 38(6), 1772-1785.
 [http://dx.doi.org/10.1080/07391102.2019.1621213] [PMID: 31107179]

[131]
Uddin, N.; Rashid, F.; Ali, S.; Tirmizi, S.A. Synthesis, characterization, and anticancer activity of Schiff bases. J. Biomol. Struct. Dyn.,  2020, 38(11), 2346-3259.
 [http://dx.doi.org/10.1080/07391102.2019.1654924] [PMID: 31411114]

[132]
Mahal, A.; Wu, P.; Jiang, Z.H.; Wei, X. Schiff bases of tetrahydrocurcumin as potential anticancer agents. Chem. Sel.,  2019, 4(1), 366-369.

[133]
Ambika, S.; Manojkumar, Y.; Arunachalam, S.; Gowdhami, B.; Meenakshi Sundaram, K.K.; Solomon, R.V.; Venuvanalingam, P.; Akbarsha, M.A.; Sundararaman, M. Biomolecular interaction, anti-cancer and anti-angiogenic properties of cobalt(III) schiff base complexes. Sci. Rep.,  2019, 9(1), 2721.
 [http://dx.doi.org/10.1038/s41598-019-39179-1] [PMID: 30804454]

[134]
Ahmad, S.N.; Bahron, H.; Tajuddin, A.M.; Ramasamy, K. Tetradentate phenolic Schiff base ligands derived from aromatic diamine and their nickel (II) complexes: Synthesis, characterization, and in vitro anticancer screening. Mal. J. Fund. Appl. Sci.,  2019, 15(4), 613-616.
 [http://dx.doi.org/10.11113/mjfas.v15n4.1508]

[135]
Deng, J.; Yu, P.; Zhang, Z.; Zhang, J.; Zhewen, S.; Cai, M.; Yuan, H.; Liang, H.; Yang, F. Novel Pt(II) complexes with modified aroyl-hydrazone Schiff-base ligands: Synthesis, cytotoxicity and action mechanism. Metallomics,  2019, 11(11), 1847-1863.
 [http://dx.doi.org/10.1039/C9MT00193J]

[136]
Slaihim, M.M.; Al-Suede, F.S.R.; Khairuddean, M.; Khadeer Ahamed, M.B.; Shah, A.M. Synthesis, characterisation of new derivatives with mono ring system of 1,2,4-triazole scaffold and their anticancer activities. J. Mol. Struct.,  2019, 1196, 78-87.
 [http://dx.doi.org/10.1016/j.molstruc.2019.06.066]

[137]
Al-Aghbari, S.A.; Al-Shuja’a, O.M.; Al-Badani, R.; Japir, A.A.W.M. Synthesis, characterization and anticancer activity studies of new schiff base Pt (II) complex. J. Mater. Sci. Chem. Eng.,  2019, 7(8), 1-8.
 [http://dx.doi.org/10.4236/msce.2019.78001]

[138]
Sahan, F.; Kose, M.; Hepokur, C.; Karakas, D.; Kurtoglu, M. New azo-azomethine-based transition metal complexes: Synthesis, spectroscopy, solid-state structure, density functional theory calculations and anticancer studies. Appl. Organomet. Chem.,  2019, 33(7), e4954.

[139]
Abd El-Razek, S.E.; El-Gamasy, S.M.; Hassan, M.; Abdel-Aziz, M.S.; Nasr, S.M. Transition metal complexes of a multidentate Schiff base ligand containing guanidine moiety: Synthesis, characterization, anti-cancer effect, and anti-microbial activity. J. Mol. Struct.,  2019, 1203, 127381.
 [http://dx.doi.org/10.1016/j.molstruc.2019.127381]

[140]
Bao, R.D.; Song, X.Q.; Kong, Y.; Li, F.F.; Liao, W.H.; Zhou, J.; Zhang, J.; Zhao, Q.H.; Xu, J.Y.; Chen, C.; Xie, M.J. A new Schiff base copper(II) complex induces cancer cell growth inhibition and apoptosis by multiple mechanisms. J. Inorg. Biochem.,  2020, 208, 111103.
 [http://dx.doi.org/10.1016/j.jinorgbio.2020.111103] [PMID: 32505045]

[141]
Li, Y.; Dong, J.; Zhao, P.; Hu, P.; Yang, D.; Gao, L.; Li, L.; Pettinari, C. Synthesis of Amino Acid Schiff Base Nickel (II) Complexes as Potential Anticancer Drugs in vitro. Bioinorg. Chem. Appl.,  2020, 2020, 8834859.
 [http://dx.doi.org/10.1155/2020/8834859] [PMID: 33061947]

[142]
Alothman, A.A.; Albaqami, M.D. Nano-sized Cu(II) and Zn(II) complexes and their use as a precursor for synthesis of CuO and ZnO nanoparticles: A study on their sonochemical synthesis, characterization, and DNA-binding/cleavage, anticancer, and antimicrobial activities. Appl. Organomet. Chem.,  2020, 34(10), e5827.
 [http://dx.doi.org/10.1002/aoc.5827]

[143]
Oliver Kappe, C. Microwave dielectric heating in synthetic organic chemistry. Chem. Soc. Rev.,  2008, 37(6), 1127-1139.
 [http://dx.doi.org/10.1039/b803001b] [PMID: 18497926]

[144]
Molteni, V.; Ellis, D. Recent advances in microwave-assisted synthesis of heterocyclic compounds. Curr. Org. Synth.,  2005, 2(3), 333-375.
 [http://dx.doi.org/10.2174/1570179054368518]

[145]
Abbass, E.M.; Khalil, A.K.; El-Naggar, A.M. Eco-friendly synthesis of novel pyrimidine derivatives as potential anticancer agents. J. Heterocycl. Chem.,  2020, 57(3), 1154-1164.
 [http://dx.doi.org/10.1002/jhet.3852]

[146]
Shiju, C.; Arish, D.; Kumaresan, S. Novel water soluble Schiff base metal complexes: Synthesis, characterization, antimicrobial-, DNA cleavage, and anticancer activity. J. Mol. Struct.,  2020, 1221, 128770.
 [http://dx.doi.org/10.1016/j.molstruc.2020.128770]

[147]
Carneiro, Z.A.; Lima, J.C.; Lopes, C.D.; Gaspari, A.P.S.; de Albuquerque, S.; Dinelli, L.R.; Veloso-Silva, L.L.W.; Paganelli, M.O.; Libardi, S.H.; Oliveira, C.G.; Deflon, V.M.; Oliveira, R.J.; Borges, J.C.; Maia, P.I.S. Heterobimetallic nickel(II) and palladium(II) complexes derived from S-benzyl-N- (ferrocenyl)methylenedithiocarbazate: Trypanocidal activity and interaction with Trypanosoma cruzi Old Yellow Enzyme (TcOYE). Eur. J. Med. Chem.,  2019, 180, 213-223.
 [http://dx.doi.org/10.1016/j.ejmech.2019.07.014] [PMID: 31306908]

[148]
Churusova, S.G.; Aleksanyan, D.V.; Rybalkina, E.Y.; Nelyubina, Y.V.; Peregudov, A.S.; Klemenkova, Z.S.; Kozlov, V.A. Non-classical N-metallated Pd(II) pincer complexes featuring amino acid pendant arms: Synthesis and biological activity. Polyhedron,  2018, 143, 70-82.
 [http://dx.doi.org/10.1016/j.poly.2017.08.019]

[149]
Alyar, S. Şen, C.; Alyar, H.; Adem, Ş.; Kalkanci, A.; Özdemir, U.O. Synthesis, characterization, antimicrobial activity, carbonic anhydrase enzyme inhibitor effects, and computational studies on new Schiff bases of Sulfa drugs and their Pd(II), Cu(II) complexes. J. Mol. Struct.,  2018, 1171, 214-222.
 [http://dx.doi.org/10.1016/j.molstruc.2018.06.004]

[150]
Farkasová, V.; Drweesh, S.A.; Lüköová, A.; Sabolová, D. Radojević,
I.D.; Čomić, L.R.; Vasić, S.M.; Paulíková, H.; Fečko, S.; Balašková, T.; Vilková, M.; Imrich, J.; Potočňák, I. Low-dimensional compounds containing bioactive ligands. Part VIII: DNA interaction, antimicrobial and antitumor activities of ionic 5,7-dihalo-8-quinolinolato palladium(II) complexes with K+ and Cs+ cations. J. Inorg. Biochem.,  2017, 167, 80-88.
 [http://dx.doi.org/10.1016/j.jinorgbio.2016.11.021] [PMID: 27912082]

[151]
Jagadeesh, M.; Rashmi, H.K.; Subba Rao, Y.; Sreenath Reddy, A.; Prathima, B.; Uma Maheswari Devi, P.; Reddy, A.V. Synthesis and spectroscopic characterization of 3,4-difluoroacetophenone-thiosemicarbazone and its palladium(II) complex: Evaluation of antimicrobial and antitumour activity. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2013, 115, 583-587.
 [http://dx.doi.org/10.1016/j.saa.2013.06.071] [PMID: 23871984]

[152]
Alyar, S.; Özmen, Ü.Ö. Adem, Ş.; Alyar, H.; Bilen, E.; Kaya, K. Synthesis, spectroscopic characterizations, carbonic anhydrase II inhibitory activity, anticancer activity and docking studies of new Schiff bases of sulfa drugs. J. Mol. Struct.,  2021, 1223, 128911.
 [http://dx.doi.org/10.1016/j.molstruc.2020.128911]

[153]
Adwin Jose, P.; Sankarganesh, M.; Dhaveethu, R.J.; Sukkur, S. Pyrimidine derivative schiff base ligand stabilized copper and nickel nanoparticles by two step phase transfer method; in vitro anticancer, antioxidant, anti-microbial and DNA interactions. J. Fluoresc.,  2020, 30(3), 471-482.
 [http://dx.doi.org/10.1007/s10895-020-02510-5]

[154]
Refaat, H.M. Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur. J. Med. Chem.,  2010, 45(7), 2949-2956.
 [http://dx.doi.org/10.1016/j.ejmech.2010.03.022] [PMID: 20399544]

[155]
Al-Hakimi, A.N.; Alminderej, F.; Aroua, L.; Alhag, S.K.; Alfaifi, M.Y.; Samir, O.M. Design, synthesis, characterization of zirconium (IV), cadmium (II) and iron (III) complexes derived from Schiff base 2-aminomethylbenzimidazole, 2-hydroxynaphtadehyde and evaluation of their biological activity. Arab. J. Chem.,  2020, 13, 7378-7389.
 [http://dx.doi.org/10.1016/j.arabjc.2020.08.014]

[156]
Liao, W.H.; Song, X.Q.; Kong, Y.J.; Bao, R.D.; Li, F.F.; Zhou, J.; Zhao, Q.H.; Xu, J.Y.; Xie, N.; Xie, M.J. A novel Schiff base cobalt(III) complex induces a synergistic effect on cervical cancer cells by arresting early apoptosis stage. Biometals,  2021, 34(2), 277-289.
 [http://dx.doi.org/10.1007/s10534-020-00278-6] [PMID: 33389333]

[157]
Almehmadi, M.A.; Aljuhani, A.; Alraqa, S.Y.; Ali, I.; Rezki, N.; Aouad, M.R.; Hagar, M. Design, synthesis, DNA binding, modeling, anticancer studies and DFT calculations of Schiff bases tethering benzothiazole-1,2,3-triazole conjugates. J. Mol. Struct.,  2021, 1225, 129148.
 [http://dx.doi.org/10.1016/j.molstruc.2020.129148]

[158]
Page, P.; Yang, L.X. Novel chemoradiosensitizers for cancer therapy. Anticancer Res.,  2010, 30(9), 3675-3682.
 [PMID: 20944153]

[159]
Bock, F.J.; Chang, P. New directions in poly(ADP-ribose) polymerase biology. FEBS J.,  2016, 283(22), 4017-4031.
 [http://dx.doi.org/10.1111/febs.13737] [PMID: 27087568]

[160]
Bryant, H.E.; Schultz, N.; Thomas, H.D.; Parker, K.M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N.J.; Helleday, T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature,  2005, 434(7035), 913-917.
 [http://dx.doi.org/10.1038/nature03443] [PMID: 15829966]

[161]
Yap, T.A.; Sandhu, S.K.; Carden, C.P.; de Bono, J.S. Poly(ADP-Ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic. CA Cancer J. Clin.,  2011, 61(1), 31-49.
 [http://dx.doi.org/10.3322/caac.20095] [PMID: 21205831]

[162]
Scully, R.; Puget, N. BRCA1 and BRCA2 in hereditary breast cancer. Biochimie,  2002, 84(1), 95-102.
 [http://dx.doi.org/10.1016/S0300-9084(01)01359-1] [PMID: 11900881]

[163]
Shridhar, D.N.; Mahendra, G.S.; Aggarwal, N.N.; Gatphoh, B.F.D.; Revanasiddappa, B.C. Insilico design, ADMET screening, MM-GBSA binding free energy of novel 1,3,4 oxadiazoles linked Schiff bases as PARP-1 inhibitors targeting breast cancer. Future J. Pharm. Sci.,  2021, 7(1), 174.
 [http://dx.doi.org/10.1186/s43094-021-00321-4]

[164]
El-Gammal, O.A.; Mohamed, F.S.; Rezk, G.N.; El-Bindary, A.A. Synthesis, characterization, catalytic, DNA binding and antibacterial activities of Co(II), Ni(II) and Cu(II) complexes with new Schiff base ligand. J. Mol. Liq.,  2021, 326, 115223.
 [http://dx.doi.org/10.1016/j.molliq.2020.115223]

[165]
Deghadi, R.G.; Abbas, A.A.; Mohamed, G.G. Theoretical and experimental investigations of new bis (amino triazole) schiff base ligand: Preparation of its UO2 (II), Er (III), and La (III) complexes, studying of their antibacterial, anticancer, and molecular docking. Appl. Organomet. Chem.,  2021, 35(8), 6292.
 [http://dx.doi.org/10.1002/aoc.6292]

[166]
Devi, J.; Yadav, J.; Lal, K.; Kumar, N.; Paul, A.K.; Kumar, D.; Dutta, P.P.; Jindal, D.K. Design, synthesis, crystal structure, molecular docking studies of some diorganotin(IV) complexes derived from the piperonylic hydrazide Schiff base ligands as cytotoxic agents. J. Mol. Struct.,  2021, 1232, 129992.
 [http://dx.doi.org/10.1016/j.molstruc.2021.129992]

[167]
Deodware, S.A.; Barache, U.B.; Chanshetti, U.B.; Sathe, D.J.; Panchsheela, A.U.; Gaikwad, S.H.; Prasad, K.S. Newly synthesized triazole-based Schiff base ligands and their Co(II) complexes as antimicrobial and anticancer agents: Chemical synthesis, structure and biological investigations. Results Chem.,  2021, 3, 100162.
 [http://dx.doi.org/10.1016/j.rechem.2021.100162]

[168]
Alkış M.E.; Keleştemür, Ü.; Alan, Y.; Turan, N.; Buldurun, K. Cobalt and ruthenium complexes with pyrimidine based schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency. J. Mol. Struct.,  2021, 1226, 129402.
 [http://dx.doi.org/10.1016/j.molstruc.2020.129402]

[169]
Serag, W.M.; Zahran, F.; Abdelghany, Y.M.; Elshaarawy, R.F.M.; Abdelhamid, M.S. Synthesis and molecular docking of hybrids ionic azole Schiff bases as novel CDK1 inhibitors and anti-breast cancer agents: in vitro and in vivo study. J. Mol. Struct.,  2021, 1245, 131041.
 [http://dx.doi.org/10.1016/j.molstruc.2021.131041]

[170]
Naureen, B.; Miana, G.A.; Shahid, K.; Asghar, M.; Tanveer, S.; Sarwar, A. Iron (III) and zinc (II) monodentate Schiff base metal complexes: Synthesis, characterisation and biological activities. J. Mol. Struct.,  2021, 1231, 129946.
 [http://dx.doi.org/10.1016/j.molstruc.2021.129946]

[171]
Alorini, T.A.; Al-Hakimi, A.N.; El-Sayed Saeed, S.; Alhamzi, E.H.L.; Albadri, A.E.A.E. Synthesis, characterization, and anticancer activity of some metal complexes with a new Schiff base ligand. Arab. J. Chem.,  2022, 15(2), 103559.
 [http://dx.doi.org/10.1016/j.arabjc.2021.103559]

[172]
Islam, M.K.; Ha, S.; Baek, A.R.; Yang, B.W.; Kim, Y.H.; Park, H.J.; Kim, M.; Nam, S.W.; Lee, G.H.; Chang, Y. The synthesis, characterization, molecular docking and in vitro antitumor Activity of Benzothiazole Aniline (BTA) conjugated metal-salen complexes as non-platinum chemotherapeutic agents. pharmaceuticals,  2022, 15(6), 751.
 [http://dx.doi.org/10.3390/ph15060751] [PMID: 35745670]

[173]
Bansal, A.; Saleh-E-In, M.M.; Kar, P.; Roy, A.; Sharma, N.R. Synthesis of carvacrol derivatives as potential new anticancer agent against lung cancer. Molecules,  2022, 27(14), 4597.
 [http://dx.doi.org/10.3390/molecules27144597] [PMID: 35889476]

[174]
Rashid, S.; Ali, N.; Nafees, S.; Ahmad, S.T.; Hasan, S.K.; Sultana, S. Abrogation of 5-flourouracil induced renal toxicity by bee propolis via targeting oxidative stress and inflammation in Wistar rats. J. Pharm. Res.,  2013, 7(2), 189-194.
 [http://dx.doi.org/10.1016/j.jopr.2013.03.003]

[175]
Famurewa, A.C.; Asogwa, N.T.; Aja, P.M.; Akunna, G.G.; Awoke, J.N.; Ekeleme-Egedigwe, C.A.; Maduagwuna, E.K.; Folawiyo, A.M.; Besong, E.E.; Ekpono, E.U.; Nwoha, P.A. Moringa oleifera seed oil modulates redox imbalance and iNOS/NF-κB/caspase-3 signaling pathway to exert antioxidant, anti-inflammatory and antiapoptotic mechanisms against anticancer drug 5-fluorouracil-induced nephrotoxicity in rats. S. Afr. J. Bot.,  2019, 127, 96-103.
 [http://dx.doi.org/10.1016/j.sajb.2019.08.038]

[176]
Savcı A.; Turan, N.; Buldurun, K.; Eşref Alkış M.; Alan, Y. Schiff base containing fluorouracil and its M(II) complexes: Synthesis, characterization, cytotoxic and antioxidant activities. Inorg. Chem. Commun.,  2022, 143, 109780.
 [http://dx.doi.org/10.1016/j.inoche.2022.109780]

[177]
Dong, J.; Li, Y.; Zhao, P.; Xu, T.; Zhang, B.; Gao, L.; Li, L. Synthesis and biological evaluation of six L-tryptophan Schiff base copper(II) complexes as promising anticancer agents in vitro. J. Mol. Struct.,  2022, 1256, 132578.
 [http://dx.doi.org/10.1016/j.molstruc.2022.132578]

[178]
Ghasemi, L.; Behzad, M.; Khaleghian, A.; Abbasi, A.; Abedi, A. Synthesis and characterization of two new mixed-ligand Cu(II) complexes of a tridentate NN’O type Schiff base ligand and N-donor heterocyclic co-ligands: In vitro anticancer assay, DNA/human leukemia/COVID-19 molecular docking studies, and pharmacophore modeling. Appl. Organomet. Chem.,  2022, 36(5), e6639.
 [http://dx.doi.org/10.1002/aoc.6639] [PMID: 35538931]

[179]
Ragole, V.D.; Gayakwad, S.V.; Wankhede, D.S. Novel Schif base (E) 2 ((4 chloro 3 nitrophenylimino) (phenyl) methyl) 5 methoxyphenol and Mixed Ligand Complexes of Mn(II), Fe(III), Co(II), Ni(II) and Cu(II): Synthesis, structure elucidation and potency study as antibacterial, antimalarial, antioxidant, antidibetic and anticancer agents. J. Indian Chem. Soc.,  2022, 19, 1993-2004.

[180]
Aroua, L.M.; Al-Hakimi, A.N.; Abdulghani, M.A.M.; Alhag, S.K. Cytotoxic urea Schiff base complexes for multidrug discovery as anticancer activity and low in vivo oral assessing toxicity. Arab. J. Chem.,  2022, 15(8), 103986.
 [http://dx.doi.org/10.1016/j.arabjc.2022.103986]

[181]
Venkateswarlu, K.; Anantha Lakshmi, P.V. Shivaraj, Synthesis, spectroscopic and thermal studies of Cu +2, Ni +2 and Co +3 complexes of Schiff base containing furan moiety. Antitumor, antioxidant, antibacterial and DNA interaction studies. Appl. Organomet. Chem.,  2022, 36(2), 6530.
 [http://dx.doi.org/10.1002/aoc.6530]

[182]
Emami, L.; Khabnadideh, S.; Faghih, Z.; Solhjoo, A.; Malek, S.; Mohammadian, A.; Divar, M.; Faghih, Z. Novel N-substituted isatin-ampyrone Schiff bases as a new class of antiproliferative agents: Design, synthesis, molecular modeling and in vitro cytotoxic activity. J. Heterocycl. Chem.,  2022, 59(7), 1144-1159.
 [http://dx.doi.org/10.1002/jhet.4454]

[183]
Gou, Y.; Jia, X.; Hou, L.X.; Deng, J.G.; Huang, G.J.; Jiang, H.W.; Yang, F. Dithiocarbazate–Fe III, -Co III, -Ni II, and -Zn II Complexes: Design, synthesis, structure, and anticancer evaluation. J. Med. Chem.,  2022, 65(9), 6677-6689.
 [http://dx.doi.org/10.1021/acs.jmedchem.1c02186] [PMID: 35446587]
Rights & Permissions Print Cite
Article Metrics
29
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1573406419666230707105221	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638
Medicinal Chemistry

An Explicative Review on the Current Advancement in Schiff Base-Metal Complexes as Anticancer Agents Evolved in the Past Decade: Medicinal Chemistry Aspects

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles
