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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

New Functionalized Morpholinothiazole Derivatives: Regioselective Synthesis, Computational Studies, Anticancer Activity Evaluation, and Molecular Docking Studies

Author(s): Mohammed A. Assiri, Tarik E. Ali*, Maha N. Alqahtani, Ibrahim A. Shaaban, Ali A. Shati, Mohammad Y. Alfaifi and Serag E.I. Elbehairi

Volume 27, Issue 22, 2023

Published on: 19 December, 2023

Page: [1985 - 1998] Pages: 14

DOI: 10.2174/0113852728274686231204053638

Price: $65

Abstract

A new series of skeletons 2-(morpholinoimino)-4,5-disubstituted-3- phenylthiazoles (2-15) was synthesized. The methodology involved the reactions of 1- morpholino-3-phenyl-thiourea (1) with a variety of α -halocarbonyl compounds under Hantzsch reaction conditions. The reaction mechanism for some postulated routes was modeled using quantum mechanical calculations in order to investigate the regioselectivity preference of this reaction in terms of thermodynamics. The quantum mechanical computations compiled with experimental IR, 1H- and 13C-NMR spectral analysis supported the favorable product, which has a thiazole ring bearing the morpholinoimino moiety at position C−2. All synthesized products were screened using the sulforhodamine B (SRB) assay for their cytotoxic properties against various cancer cell lines. Fortunately, the target compounds 2, 4, 5, 6, 11, and 12 were discovered to be comparable to doxorubicin in terms of their potency against all evaluated cell lines. Utilizing flow cytometry, apoptosis and cell cycle analyses were determined and supported by molecular docking studies. All tumor cells were significantly early- and late-apoptotic affected by the products 2, 4, 5, 6, 11 and 12, and these products also significantly halted all studied types of cancer cells in both S and G2 phases. The discovered compounds 2 and 12 were then subjected to a molecular docking experiment to examine how they bind with the VEGFR-2-KDR receptor.

Keywords: Morpholine, thiazole, cytotoxicity, molecular docking, antiparasitic, antidepressant.

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[1]
Wang, Y.; Gu, W.; Shan, Y.; Liu, F.; Xu, X.; Yang, Y.; Zhang, Q.; Zhang, Y.; Kuang, H.; Wang, Z.; Wang, S. Design, synthesis and anticancer activity of novel nopinone-based thiosemicarbazone derivatives. Bioorg. Med. Chem. Lett., 2017, 27(11), 2360-2363.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.024] [PMID: 28431878]
[2]
El-Sherief, H.A.M.; Youssif, B.G.M.; Bukhari, S.N.A.; Abdel-Aziz, M.; Abdel-Rahman, H.M. Novel 1,2,4-triazole derivatives as potential anticancer agents: Design, synthesis, molecular docking and mechanistic studies. Bioorg. Chem., 2018, 76, 314-325.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.013] [PMID: 29227915]
[3]
McGuire, S. World cancer report 2014. geneva, switzerland: World health organization, international agency for research on cancer, WHO press, 2015. Adv. Nutr., 2016, 7(2), 418-419.
[http://dx.doi.org/10.3945/an.116.012211] [PMID: 26980827]
[4]
Simpson, C.D.; Anyiwe, K.; Schimmer, A.D. Anoikis resistance and tumor metastasis. Cancer Lett., 2008, 272(2), 177-185.
[http://dx.doi.org/10.1016/j.canlet.2008.05.029] [PMID: 18579285]
[5]
Berger, M.F.; Mardis, E.R. The emerging clinical relevance of genomics in cancer medicine. Nat. Rev. Clin. Oncol., 2018, 15(6), 353-365.
[http://dx.doi.org/10.1038/s41571-018-0002-6] [PMID: 29599476]
[6]
Hoelder, S.; Clarke, P.A.; Workman, P. Discovery of small molecule cancer drugs: Successes, challenges and opportunities. Mol. Oncol., 2012, 6(2), 155-176.
[http://dx.doi.org/10.1016/j.molonc.2012.02.004] [PMID: 22440008]
[7]
Li, L.; Liu, S.; Wang, B.; Liu, F.; Xu, S.; Li, P.; Chen, Y. An updated review on developing small molecule kinase inhibitors using computer-aided drug design approaches. Int. J. Mol. Sci., 2023, 24(18), 13953.
[http://dx.doi.org/10.3390/ijms241813953] [PMID: 37762253]
[8]
Sharma, A.; Shambhwani, D.; Pandey, S.; Singh, J.; Lalhlenmawia, H.; Kumarasamy, M.; Singh, S.K.; Chellappan, D.K.; Gupta, G.; Prasher, P.; Dua, K.; Kumar, D. Advances in lung cancer treatment using nanomedicines. ACS Omega, 2023, 8(1), 10-41.
[http://dx.doi.org/10.1021/acsomega.2c04078] [PMID: 36643475]
[9]
Moinul, M.; Khatun, S.; Amin, S.A.; Jha, T.; Gayen, S. Recent trends in fragment-based anticancer drug design strategies against different targets: A mini-review. Biochem. Pharmacol., 2022, 206, 115301.
[http://dx.doi.org/10.1016/j.bcp.2022.115301] [PMID: 36265594]
[10]
Agarwal, S.; Sane, R.; Oberoi, R.; Ohlfest, J.R.; Elmquist, W.F. Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain. Expert Rev. Mol. Med., 2011, 13, e17.
[http://dx.doi.org/10.1017/S1462399411001888] [PMID: 21676290]
[11]
Gul, H.I.; Yamali, C.; Sakagami, H.; Angeli, A.; Leitans, J.; Kazaks, A.; Tars, K.; Ozgun, D.O.; Supuran, C.T. New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors. Bioorg. Chem., 2018, 77, 411-419.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.021] [PMID: 29427856]
[12]
Elmetwally, S.A.; Saied, K.F.; Eissa, I.H.; Elkaeed, E.B. Design, synthesis and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers. Bioorg. Chem., 2019, 88, 102944.
[http://dx.doi.org/10.1016/j.bioorg.2019.102944] [PMID: 31051400]
[13]
Milik, S.N.; Abdel-Aziz, A.K.; Lasheen, D.S.; Serya, R.A.T.; Minucci, S.; Abouzid, K.A.M. Surmounting the resistance against EGFR inhibitors through the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors. Eur. J. Med. Chem., 2018, 155, 316-336.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.011] [PMID: 29902719]
[14]
Saroha, B.; Kumar, G.; Kumar, R.; Kumari, M.; Kumar, S. A minireview of 1,2,3‐triazole hybrids with O‐heterocycles as leads in medicinal chemistry. Chem. Biol. Drug Des., 2022, 100(6), 843-869.
[http://dx.doi.org/10.1111/cbdd.13966] [PMID: 34592059]
[15]
Claudio Viegas-Junior. Danuello, A.; da Silva Bolzani, V.; Barreiro, E.J.; Fraga, C.A.M. Molecular hybridization: A useful tool in the design of new drug prototypes. Curr. Med. Chem., 2007, 14(17), 1829-1852.
[http://dx.doi.org/10.2174/092986707781058805] [PMID: 17627520]
[16]
Kumar, G.; Saroha, B.; Kumar, R.; Kumari, M.; Kumar, S. Recent advances in synthesis and biological assessment of quinoline‐oxygen heterocycle hybrids. ChemistrySelect, 2021, 6(20), 5148-5165.
[http://dx.doi.org/10.1002/slct.202100906]
[17]
Lazar, C.; Kluczyk, A.; Kiyota, T.; Konishi, Y. Drug evolution concept in drug design: 1. Hybridization method. J. Med. Chem., 2004, 47(27), 6973-6982.
[http://dx.doi.org/10.1021/jm049637+] [PMID: 15615546]
[18]
Taghour, M.S.; Elkady, H.; Eldehna, W.M.; El-Deeb, N.M.; Kenawy, A.M.; Elkaeed, E.B.; Alsfouk, A.A.; Alesawy, M.S.; Metwaly, A.M.; Eissa, I.H. Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: In-vitro anticancer evaluation and in-silico studies. J. Enzyme Inhib. Med. Chem., 2022, 37(1), 1903-1917.
[http://dx.doi.org/10.1080/14756366.2022.2085693] [PMID: 35801403]
[19]
Elkaeed, E.B.; Yousef, R.G.; Elkady, H.; Gobaara, I.M.M.; Alsfouk, A.A.; Husein, D.Z.; Ibrahim, I.M.; Metwaly, A.M.; Eissa, I.H. The assessment of anticancer and VEGFR-2 ınhibitory activities of a new 1H-ındole derivative: In silico and in vitro approaches. Processes, 2022, 10(7), 1391.
[http://dx.doi.org/10.3390/pr10071391]
[20]
Qi, B.; Yang, Y.; He, H.; Yue, X.; Zhou, Y.; Zhou, X.; Chen, Y.; Liu, M.; Zhang, A.; Wei, F. Identification of novel N-(2-aryl-1,3-thiazolidin-4-one)-N-aryl ureas showing potent multi-tyrosine kinase inhibitory activities. Eur. J. Med. Chem., 2018, 146, 368-380.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.061] [PMID: 29407963]
[21]
Hassan, E.A.; Shehadi, I.A.; Elmaghraby, A.M.; Mostafa, H.M.; Zayed, S.E.; Abdelmonsef, A.H. Synthesis, molecular docking analysis and in vitro biological evaluation of some new heterocyclic scaffolds-based indole moiety as possible antimicrobial agents. Front. Mol. Biosci., 2022, 8, 775013.
[http://dx.doi.org/10.3389/fmolb.2021.775013] [PMID: 35111810]
[22]
Abu-Melha, S.; Edrees, M.; Salem, H.; Kheder, N.; Gomha, S.; Abdelaziz, M. Synthesis and biological evaluation of some novel thiazole-based heterocycles as potential anticancer and antimicrobial agents. Molecules, 2019, 24(3), 539.
[http://dx.doi.org/10.3390/molecules24030539] [PMID: 30717217]
[23]
Nayak, S.; Gaonkar, S.L. A review on recent synthetic strategies and pharmacological importance of 1,3-thiazole derivatives. Mini Rev. Med. Chem., 2019, 19(3), 215-238.
[http://dx.doi.org/10.2174/1389557518666180816112151] [PMID: 30112994]
[24]
Gomha, S.M.; Salah, T.A.; Abdelhamid, A.O. Synthesis, characterization, and pharmacological evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as anticancer agents. Monatsh. Chem., 2015, 146(1), 149-158.
[http://dx.doi.org/10.1007/s00706-014-1303-9]
[25]
dos Santos Silva, T.D.; Bomfim, L.M.; da Cruz Rodrigues, A.C.B.; Dias, R.B.; Sales, C.B.S.; Rocha, C.A.G.; Soares, M.B.P.; Bezerra, D.P.; de Oliveira Cardoso, M.V.; Leite, A.C.L.; Militão, G.C.G. Anti-liver cancer activity in vitro and in vivo induced by 2-pyridyl 2,3-thiazole derivatives. Toxicol. Appl. Pharmacol., 2017, 329, 212-223.
[http://dx.doi.org/10.1016/j.taap.2017.06.003] [PMID: 28610992]
[26]
Naim, M.J.; Alam, O.; Alam, M.J.; Alam, P.; Shrivastava, N. A review on pharmacological profile of morpholine derivatives. Int. J. Pharm. Pharm. Sci., 2015, 3, 40-51.
[27]
Sameem, B.; Saeedi, M.; Mahdavi, M.; Nadri, H.; Moghadam, F.H.; Edraki, N.; Khan, M.I.; Amini, M. Synthesis, docking study and neuroprotective effects of some novel pyrano[3,2-c]chromene derivatives bearing morpholine/phenylpiperazine moiety. Bioorg. Med. Chem., 2017, 25(15), 3980-3988.
[http://dx.doi.org/10.1016/j.bmc.2017.05.043] [PMID: 28587871]
[28]
Polshettiwar, V.; Varma, R.S. Greener and expeditious synthesis of bioactive heterocycles using microwave irradiation. Pure Appl. Chem., 2008, 80(4), 777-790.
[http://dx.doi.org/10.1351/pac200880040777]
[29]
Zaharia, V.; Silvestru, A.; Palibroda, N.; Mogosan, C. Heterocycles 28. synthesis and characterization of some bis and polyhetererocyclic compounds with anti-inflammatory potential. Farmacia, 2011, 59, 624-635.
[30]
Wu, Y.J.; Meanwell, N.A. Geminal diheteroatomic motifs: Some applications of acetals, ketals, and their sulfur and nitrogen homologues in medicinal chemistry and drug design. J. Med. Chem., 2021, 64(14), 9786-9874.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00790] [PMID: 34213340]
[31]
Arshad, F.; Khan, M.F.; Akhtar, W.; Alam, M.M.; Nainwal, L.M.; Kaushik, S.K.; Akhter, M.; Parvez, S.; Hasan, S.M.; Shaquiquzzaman, M. Revealing quinquennial anticancer journey of morpholine: A SAR based review. Eur. J. Med. Chem., 2019, 167, 324-356.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.015] [PMID: 30776694]
[32]
Ali, T.E.; Assiri, M.A.; Alzahrani, A.Y.; Salem, M.A.; Shati, A.A.; Alfaifi, M.Y.; Elbehairi, S.E.I. An effective green one-pot synthesis of some novel 5-(thiophene-2-carbonyl)-6-(trifluoromethyl)pyrano[2,3-c]pyrazoles and 6-(thiophene-2-carbonyl)-7-(trifluoromethyl)pyrano[2,3-d]pyrimidines bearing chromone ring as anticancer agents. Synth. Commun., 2021, 51(21), 3267-3276.
[http://dx.doi.org/10.1080/00397911.2021.1966804]
[33]
Ali, T.E.; Assiri, M.A.; Shati, A.A.; Alfaifi, M.Y.; Elbehairi, S.E.I. One-pot three-component synthesis of a series of 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(2,2,2-trifluoroacetyl)-6-(trifluoromethyl)-4H-pyrans and 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(thiophene-2-carbonyl)-6-(trifluoromethyl)-4H-pyrans as promising anticancer agents. Russ. J. Org. Chem., 2022, 58(4), 584-591.
[http://dx.doi.org/10.1134/S1070428022040170]
[34]
Assiri, M.A.; Ali, T.E.; Alqahtani, M.N.; Shati, A.A.; Alfaifi, M.Y.; Elbehairi, S.E.I. Synthesis, cytotoxic evaluation, apoptosis, cell cycle, and molecular docking studies of some new 5-(arylidene/heteroarylidene)-2-(morpholinoimino)-3-phenylthiazolidin-4-ones. Synth. Commun., 2023, 53(15), 1240-1261.
[http://dx.doi.org/10.1080/00397911.2023.2217963]
[35]
Ali, T.E.; Assiri, M.A.; Alqahtani, M.N.; Shati, A.A.; Alfaifi, M.Y.; Elbehairi, S.E.I. Recyclization of morpholinochromonylidene–thiazolidinone using nucleophiles: Facile synthesis, cytotoxic evaluation, apoptosis, cell cycle and molecular docking studies of a novel series of azole, azine, azepine and pyran derivatives. RSC Advances, 2023, 13(27), 18658-18675.
[http://dx.doi.org/10.1039/D3RA02777E] [PMID: 37346943]
[36]
Spillier, Q.; Ravez, S.; Unterlass, J.; Corbet, C.; Degavre, C.; Feron, O.; Frédérick, R. Structure–activity relationships (SARs) of α-Ketothioamides as inhibitors of phosphoglycerate dehydrogenase (PHGDH). Pharmaceuticals, 2020, 13(2), 20.
[http://dx.doi.org/10.3390/ph13020020] [PMID: 31979167]
[37]
Facchinetti, V.; Avellar, M.M.; Nery, A.C.S.; Gomes, C.R.B.; Vasconcelos, T.R.A.; de Souza, M.V.N. An eco-friendly, hantzsch-based, solvent-free approach to 2-amino-thiazoles and 2-aminoselenazoles. Synthesis, 2016, 48, 437-440.
[38]
Becke, A.D. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A Gen. Phys., 1988, 38(6), 3098-3100.
[http://dx.doi.org/10.1103/PhysRevA.38.3098] [PMID: 9900728]
[39]
Lee, C.; Yang, W.; Parr, R.G. Development of the colle-salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B Condens. Matter, 1988, 37(2), 785-789.
[http://dx.doi.org/10.1103/PhysRevB.37.785] [PMID: 9944570]
[40]
Frisch, M.; Trucks, G.; Schlegel, H.; Scuseria, G.; Robb, M.; Cheeseman, J.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.; Izmaylov, A.; Bloino, J.; Zheng, G.; Sonnenberg, J.; Hada, M.; Fox, D. Gaussian 09 (Revision A02); Gaussian Inc.: Wallingford, CT, 2009.
[41]
Pulay, P. Ab initio calculation of force constants and equilibrium geometries in polyatomic molecules. Mol. Phys., 1969, 17(2), 197-204.
[http://dx.doi.org/10.1080/00268976900100941]
[42]
Borba, A.; Albrecht, M.; Gómez-Zavaglia, A.; Lapinski, L.; Nowak, M.J.; Suhm, M.A.; Fausto, R. Dimer formation in nicotinamide and picolinamide in the gas and condensed phases probed by infrared spectroscopy. Phys. Chem. Chem. Phys., 2008, 10(46), 7010-7021.
[http://dx.doi.org/10.1039/b810002k] [PMID: 19030597]
[43]
Tomasi, J.; Mennucci, B.; Cancès, E. The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level. J. Mol. Struct. THEOCHEM, 1999, 464(1-3), 211-226.
[http://dx.doi.org/10.1016/S0166-1280(98)00553-3]
[44]
Ditchfield, R. Self-consistent perturbation theory of diamagnetism. Mol. Phys., 1974, 27(4), 789-807.
[http://dx.doi.org/10.1080/00268977400100711]
[45]
Chesnut, D.B.; Phung, C.G. Nuclear magnetic resonance chemical shifts using optimized geometries. J. Chem. Phys., 1989, 91(10), 6238-6245.
[http://dx.doi.org/10.1063/1.457390]
[46]
Sarotti, A.M.; Pellegrinet, S.C. A multi-standard approach for GIAO (13)C NMR calculations. J. Org. Chem., 2009, 74(19), 7254-7260.
[http://dx.doi.org/10.1021/jo901234h] [PMID: 19725561]
[47]
Sarotti, A.M.; Pellegrinet, S.C. Application of the multi-standard methodology for calculating 1H NMR chemical shifts. J. Org. Chem., 2012, 77(14), 6059-6065.
[http://dx.doi.org/10.1021/jo3008447] [PMID: 22713105]
[48]
Gomha, S.M.; Khalil, K.D. A convenient ultrasound-promoted synthesis of some new thiazole derivatives bearing a coumarin nucleus and their cytotoxic activity. Molecules, 2012, 17(8), 9335-9347.
[http://dx.doi.org/10.3390/molecules17089335] [PMID: 22864241]
[49]
El-Helw, E.A.E.; Sallam, H.A.; Elgubbi, A.S. Antioxidant activity of some N-heterocycles derived from 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene) hydrazinecarbothioamide. Synth. Commun., 2019, 49(20), 2651-2661.
[http://dx.doi.org/10.1080/00397911.2019.1638938]
[50]
Berseneva, V.S.; Tkachev, A.V.; Morzherin, Y.Y.; Dehaen, W.; Luyten, I.; Toppet, S.; Bakulev, V.A. Synthesis of novel thiazolidin-4-ones by reaction of malonthioamide derivatives with dimethyl acetylenedicarboxylate. J. Chem. Soc., Perkin Trans. 1, 1998, (14), 2133-2136.
[http://dx.doi.org/10.1039/a803543a]
[51]
Maslen, H.L.; Hughes, D.; Hursthouse, M.; De Clercq, E.; Balzarini, J.; Simons, C. 6-Azapyrimidine-2‘-deoxy-4‘-thionucleosides: Antiviral agents against TK+ and TK− HSV and VZV strains. J. Med. Chem., 2004, 47(22), 5482-5491.
[http://dx.doi.org/10.1021/jm049806q] [PMID: 15481985]
[52]
Mahmoud, A.M.; Al-Abd, A.M.; Lightfoot, D.A.; El-Shemy, H.A. Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent. J. Enzyme Inhib. Med. Chem., 2012, 27(5), 673-679.
[http://dx.doi.org/10.3109/14756366.2011.607446] [PMID: 21883038]
[53]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[54]
Fesik, S.W. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer, 2005, 5(11), 876-885.
[http://dx.doi.org/10.1038/nrc1736] [PMID: 16239906]
[55]
Bashmail, H.A.; Alamoudi, A.A.; Noorwali, A.; Hegazy, G.A. AJabnoor, G.; Choudhry, H.; Al-Abd, A.M. Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities. Sci. Rep., 2018, 8(1), 11674.
[http://dx.doi.org/10.1038/s41598-018-30046-z] [PMID: 30076320]
[56]
Kutwin, M.; Sawosz, E.; Jaworski, S.; Wierzbicki, M.; Strojny, B.; Grodzik, M.; Ewa Sosnowska, M.; Trzaskowski, M.; Chwalibog, A. Nanocomplexes of graphene oxide and platinum nanoparticles against colorectal cancer Colo205, HT-29, HTC-116, SW480, Liver Cancer HepG2, human breast cancer MCF-7, and adenocarcinoma LNCaP and human cervical hela B cell lines. Materials, 2019, 12(6), 909.
[http://dx.doi.org/10.3390/ma12060909] [PMID: 30893818]
[57]
Bendale, Y.; Bendale, V.; Paul, S. Evaluation of cytotoxic activity of platinum nanoparticles against normal and cancer cells and its anticancer potential through induction of apoptosis. Integr. Med. Res., 2017, 6(2), 141-148.
[http://dx.doi.org/10.1016/j.imr.2017.01.006] [PMID: 28664137]
[58]
Nunez, R. DNA measurement and cell cycle analysis by flow cytometry. Curr. Issues Mol. Biol., 2001, 3(3), 67-70.
[PMID: 11488413]
[59]
Williams, G.H.; Stoeber, K. The cell cycle and cancer. J. Pathol., 2012, 226(2), 352-364.
[http://dx.doi.org/10.1002/path.3022] [PMID: 21990031]
[60]
Siritutsoontorn, S.; Sukjoi, W.; Polyak, S.W.; Akekawatchai, C.; Jitrapakdee, S. Differential growth inhibition, cell cycle arrest and apoptosis of MCF-7 and MDA-MB-231 cells to holocarboxylase synthetase suppression. Biochem. Biophys. Res. Commun., 2022, 593, 108-115.
[http://dx.doi.org/10.1016/j.bbrc.2022.01.049] [PMID: 35063765]
[61]
Stewart, Z.A.; Westfall, M.D.; Pietenpol, J.A. Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol. Sci., 2003, 24(3), 139-145.
[http://dx.doi.org/10.1016/S0165-6147(03)00026-9] [PMID: 12628359]
[62]
Shweiki, D.; Itin, A.; Soffer, D.; Keshet, E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature, 1992, 359(6398), 843-845.
[http://dx.doi.org/10.1038/359843a0] [PMID: 1279431]
[63]
McMahon, G. VEGF receptor signaling in tumor angiogenesis. Oncologist, 2000, 5(S1)(Suppl. 1), 3-10.
[http://dx.doi.org/10.1634/theoncologist.5-suppl_1-3] [PMID: 10804084]
[64]
Forsythe, J.A.; Jiang, B.H.; Iyer, N.V.; Agani, F.; Leung, S.W.; Koos, R.D.; Semenza, G.L. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol. Cell. Biol., 1996, 16(9), 4604-4613.
[http://dx.doi.org/10.1128/MCB.16.9.4604] [PMID: 8756616]
[65]
Ikeda, E.; Achen, M.G.; Breier, G.; Risau, W. Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J. Biol. Chem., 1995, 270(34), 19761-19766.
[http://dx.doi.org/10.1074/jbc.270.34.19761] [PMID: 7544346]
[66]
Abdullah, S.E.; Perez-Soler, R. Mechanisms of resistance to vascular endothelial growth factor blockade. Cancer, 2012, 118(14), 3455-3467.
[http://dx.doi.org/10.1002/cncr.26540] [PMID: 22086782]
[67]
Yang, C.; Guo, Y.; Jadlowiec, C.C.; Li, X.; Lv, W.; Model, L.S.; Collins, M.J.; Kondo, Y.; Muto, A.; Shu, C.; Dardik, A. Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells. J. Surg. Res., 2013, 183(1), 478-486.
[http://dx.doi.org/10.1016/j.jss.2013.01.009] [PMID: 23394931]
[68]
Modi, S.J.; Kulkarni, V.M. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: Medicinal chemistry perspective. Med. Drug Discovery, 2019, 2, 100009.
[http://dx.doi.org/10.1016/j.medidd.2019.100009]
[69]
Cee, V.J.; Cheng, A.C.; Romero, K.; Bellon, S.; Mohr, C.; Whittington, D.A.; Bak, A.; Bready, J.; Caenepeel, S.; Coxon, A.; Deak, H.L.; Fretland, J.; Gu, Y.; Hodous, B.L.; Huang, X.; Kim, J.L.; Lin, J.; Long, A.M.; Nguyen, H.; Olivieri, P.R.; Patel, V.F.; Wang, L.; Zhou, Y.; Hughes, P.; Geuns-Meyer, S. Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase. Bioorg. Med. Chem. Lett., 2009, 19(2), 424-427.
[http://dx.doi.org/10.1016/j.bmcl.2008.11.056] [PMID: 19062275]
[70]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19(14), 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[71]
Huey, R.; Morris, G.M.; Olson, A.J.; Goodsell, D.S. A semiempirical free energy force field with charge‐based desolvation. J. Comput. Chem., 2007, 28(6), 1145-1152.
[http://dx.doi.org/10.1002/jcc.20634] [PMID: 17274016]
[72]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and autodocktools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[73]
Trott, O.; Olson, A.J. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]
[74]
Eberhardt, J.; Santos-Martins, D.; Tillack, A.F.; Forli, S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model., 2021, 61(8), 3891-3898.
[http://dx.doi.org/10.1021/acs.jcim.1c00203] [PMID: 34278794]
[75]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-A visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]

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