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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis and Biological Evaluation of 4-Aminoantipyrine Analogues

Author(s): Houwei Ren, Premnath Dhanaraj*, Israel V.M.V. Enoch*, Mosae Selvakumar Paulraj and Indiraleka M.

Volume 18, Issue 1, 2022

Published on: 05 November, 2020

Page: [26 - 35] Pages: 10

DOI: 10.2174/1573406416666201106105303

Price: $65

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Abstract

Objectives: The aim of the present study is to carry out a simple synthesis of aminoantipyrine analogues and exploration of their antibacterial, cytotoxic, and anticonvulsant potential.

Methods: The compounds were characterized employing multi-spectroscopic methods. The in vitro pharmacological response of a series of bacteria was screened employing serial dilution method. The derivatives were screened against maximal electro-shock for their anticonvulsant activity. Molecular docking was carried out to optimize the interaction of the compounds with HPV16-E7 receptors. Further, the in vitro cytotoxicity was tested against human cervical cancer (SiHa) cell lines.

Results: The compounds show protection against maximal electroshock, esp. 3-nirto- and 4- methyl-3-nitrobenzamido derivatives. In addition, they reveal appreciable DNA cleavage activities and interactions with HPV16-E7 protein receptors, esp. 3,5-dinitro- and 4-methyl-3-nitrobenzamido derivatives. Furthermore, they show potent activity against cervical cancer cells (LD50 value up to 1200 in the case of 4-methyl-3-nitrobenzamido derivative and an inhibition of a maximum of ~97% of cells).

Conclusion: The simply synthesized aminoantipyrine derivatives show a variety of biological activities like antibacterial and anticancer effects. In addition, this is the first study demonstrating that 4-aminoantipyrine derivatives show an anticonvulsant activity.

Keywords: 4-Aminoantipyridine, spectroscopy, anticonvulsant, antibacterial, cytotoxicity, molecular docking.

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[1]
Sahoo, J.; Sahoo, C.R.; Nandini Sarangi, P.K.; Prusty, S.K.; Padhy, R.N.; Paidesetty, S.K. Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore. Eur. J. Med. Chem., 2020.186111911
[http://dx.doi.org/10.1016/j.ejmech.2019.111911] [PMID: 31791644]
[2]
Ali, P.; Meshram, J.; Sheikh, J.; Tiwari, V.; Dongre, R.; Hadda, T.B. Predictions and correlations of structure activity relationship of some aminoantipyrine derivatives on the basis of theoretical and experimental ground. Med. Chem. Res., 2012, 21, 157-164.
[http://dx.doi.org/10.1007/s00044-010-9505-0]
[3]
Elattar, K.M.; Fadda, A.A. Chemistry of antipyrine. Synth. Commun., 2016, 46, 1567-1594.
[http://dx.doi.org/10.1080/00397911.2016.1211703]
[4]
Fathima, S.S.A.; Paulpandiyan, R.; Nagarajan, E.R. Expatiating biological excellence of aminoantipyrine derived novel metal complexes: Combined DNA interaction, antimicrobial, free radical scavenging studies and molecular docking simulations. J. Mol. Struct., 2019, 1178, 179-191.
[http://dx.doi.org/10.1016/j.molstruc.2018.10.021]
[5]
Boudergua, S.; Alloui, M.; Belaidi, S.; Mogren, M.A.; Ibrahim, U.A.A.E.; Hochlaf, M. QSAR Modeling and drug-likeness screening for antioxidant activity of benzofuran derivatives. J. Mol. Struct., 2019, 1189, 307-314.
[http://dx.doi.org/10.1016/j.molstruc.2019.04.004]
[6]
Saeed, A.; Ejaz, S.A.; Khurshid, A.; Hassan, S.; Al-Rashida, M.; Latif, M.; Lecka, J.; Sévignyef, J.; Iqbal, J. Synthesis, characterization and biological evaluation of N-(2,3-dimethyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-4-yl)benzamides. RSC Advances, 2015, 5, 86428-86439.
[http://dx.doi.org/10.1039/C5RA17568B]
[7]
Malik, M.A.; Dar, O.A.; Gull, P.; Wani, M.Y.; Hashmi, A.A. Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. MedChemComm, 2017, 9(3), 409-436.
[http://dx.doi.org/10.1039/C7MD00526A] [PMID: 30108933]
[8]
Ghorab, M.M.; El-Gazzar, M.G.; Alsaid, M.S. Synthesis, characterization and anti-breast cancer activity of new 4-aminoantipyrine-based heterocycles. Int. J. Mol. Sci., 2014, 15(5), 7539-7553.
[http://dx.doi.org/10.3390/ijms15057539] [PMID: 24798749]
[9]
Ventola, C.L. The antibiotic resistance crisis: part 1: causes and threats. P&T, 2015, 40(4), 277-283.
[PMID: 25859123]
[10]
Subramani, R.; Narayanasamy, M.; Feussner, K. D. Plant-derived antimicrobials to fight against multi-drug-resistant human pathogens 3 Biotech, 2017, 7, 172.
[11]
Tsuda, N.; Watari, H.; Ushijima, K. Chemotherapy and molecular targeting therapy for recurrent cervical cancer. Chin. J. Cancer Res., 2016, 28(2), 241-253.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2016.02.14] [PMID: 27199523]
[12]
de Souza, I.P.; Machado, B.P.; de Carvalho, A.B.; Binatti, I.; Krambrock, K.; Molphy, Z.; Kellett, A.; Pereira-Maia, A.C.; Silva-Caldeira, P.P. Exploring the DNA binding, oxidative cleavage, and cytotoxic properties of new ternary copper(II) compounds containing 4-aminoantipyrine and N,N-heterocyclic co-ligands. J. Mol. Struct., 2019, 1178, 18-28.
[http://dx.doi.org/10.1016/j.molstruc.2018.10.004]
[13]
Elashal, H.E.; Raj, M. Site-selective chemical cleavage of peptide bonds. Chem. Commun. (Camb.), 2016, 52(37), 6304-6307.
[http://dx.doi.org/10.1039/C6CC01509C] [PMID: 27087443]
[14]
Frutos, S.; Goger, M.; Giovani, B.; Cowburn, D.; Muir, T.W. Branched intermediate formation stimulates peptide bond cleavage in protein splicing. Nat. Chem. Biol., 2010, 6(7), 527-533.
[http://dx.doi.org/10.1038/nchembio.371] [PMID: 20495572]
[15]
Mohanram, I.; Meshram, J. Synthesis and biological activities of 4-aminoantipyrine derivatives derived from betti-type reaction. ISRN Org. Chem., 2014.2014639392
[http://dx.doi.org/10.1155/2014/639392] [PMID: 24955256]
[16]
Alam, M.S.; Lee, D.U.; Bari, M.L. Antibacterial and cytotoxic activities of Schiff base analogues of 4-aminoantipyrine. J. Korean Soc. Appl. Biol. Chem., 2014, 57, 613-619.
[http://dx.doi.org/10.1007/s13765-014-4201-2]
[17]
Emam, S.M.; Abouel‐Enein, S.A.; Abouzayed, F.I. Synthesis, spectral characterization, thermal studies and biological activity of (Z)‐5‐((1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyraz ol‐4‐yl)diazenyl)‐6‐hydroxy‐2‐mercaptopyrimidin‐4(3H)‐one and its metal complexes. Appl. Organomet. Chem. 2018. 32e4073
[http://dx.doi.org/10.1002/aoc.4073]
[18]
Pal, A.; Kundu, R. Human papillomavirus E6 and E7: the cervical cancer hallmarks and targets for therapy. Front. Microbiol., 2020, 10, 3116.
[http://dx.doi.org/10.3389/fmicb.2019.03116] [PMID: 32038557]
[19]
Dizanzo, M. P.; Marziali, F.; Avalos, C. B.; Valdano, M. B.; Leiva, S.; Cavatorta, A. L.; Gardiol, D. HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells, 2020, 20
[20]
Schutz, F.A.B.; Choueiri, T.K.; Sternberg, C.N. Pazopanib: Clinical development of a potent anti-angiogenic drug. Crit. Rev. Oncol. Hematol., 2011, 77(3), 163-171.
[http://dx.doi.org/10.1016/j.critrevonc.2010.02.012] [PMID: 20456972]
[21]
Deng, X.Q.; Song, M.X.; Wei, C.X.; Li, F.N.; Quan, Z.S. Synthesis and anticonvulsant activity of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Med. Chem., 2010, 6(5), 313-320.
[http://dx.doi.org/10.2174/157340610793358855] [PMID: 20977415]
[22]
Dong, Z-Q.; Liu, X-M.; Wei, C-X.; Quan, Z.S. Design, synthesis of 6-substituted-pyrido[3,2-d]pyridazine derivatives with anticonvulsant activity. Med. Chem., 2015, 11(6), 595-601.
[http://dx.doi.org/10.2174/1573406411666150313152925] [PMID: 25770755]

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