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Synthesis and Evaluation of 1,2,4-Triazole Derivatives for Antioxidant, Anti-inflammatory, Cytotoxicity and QSAR Analysis
Corresponding Author(s) : Shaheen Begum
Asian Journal of Chemistry,
Vol. 35 No. 1 (2023): Vol 35 Issue 1
Abstract
A series of novel 4-amino-5-substituted-1,2,4-triazole-3-thiol derivatives (B1-B18) were synthesized and characterized by spectral analysis. Equimolar portions of thiocarbohydrazide and different acids (substituted aryl/heteroaryl/aliphatic) were fused to synthesize the title compounds. The compounds were evaluated for cytotoxicity, in vitro anti-inflammatory activity and antioxidant activities. Cytotoxicity studies highlighted B4 (2,4-dichloro analog) as the potent cytotoxic molecule with IC50 value of 20.35 μM against MCF-7 cell line compared to cisplatin (IC50 = 12.06 μM). B4 (2,4-dichloro), B18 (oleayl) and B14 (2-hydroxy) showed significant membrane-stabilizing activity with IC50 values < 35 μM, whereas B11 (3,4-dimethoxy), B4 (2,4-dichloro) and B14 (2-hydroxy) displayed moderate proteinase inhibitory activity with IC50 values < 72 μM. Compounds possessing phenolic hydroxyl group (B12−B14) demonstrated an appreciable antioxidant activity in the studied antioxidant models. QSAR analysis revealed the important contribution of molecular connectivity, ionization potential and mass of the compounds for optimum cytotoxicity. Present results suggested compound B4 as a potential lead molecule to design novel and potent cytotoxic and anti-inflammatory agents.
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- N. Sreejayan and M. Rao, J. Pharm. Pharmacol., 49, 105 (1997); https://doi.org/10.1111/j.2042-7158.1997.tb06761.x
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T.A. Moo, R. Sanford, C. Dang and M. Morrow, PET Clin., 13, 339 (2018); https://doi.org/10.1016/j.cpet.2018.02.006
R. Kaur, A. Ranjan Dwivedi, B. Kumar and V. Kumar, Anticancer. Agents Med. Chem., 16, 465 (2016); https://doi.org/10.2174/1871520615666150819121106
S. Kumar, S.L. Khokra and A. Yadav, Futur. J. Pharm. Sci., 7, 106 (2021); https://doi.org/10.1186/s43094-021-00241-3
M. Koparir, A. Cansiz and A. Demirdag, Molecules, 9, 204 (2004); https://doi.org/10.3390/90400204
M.A. Kaldrikyan, N.S. Minasyan and R.G. Melik-Ogandzhanyan, Russ. J. Gen. Chem., 85, 622 (2015); https://doi.org/10.1134/S1070363215030160
A.K. Gupta, S. Prachand, A. Patel and S. Jain, Int. J. Pharm. Life Sci., 3, 1848 (2012).
A.T.A. Boraei, P.K. Singh, M. Sechi and S. Satta, Eur. J. Med. Chem.,182, 111621 (2019); https://doi.org/10.1016/j.ejmech.2019.111621
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V. Prachayasittikul, N. Anuwongcharoen, A. Worachartcheewan, C. Nantasenamat, R. Pingaew, S. Prachayasittikul, S. Ruchirawat and V. Prachayasittikul, Springerplus, 4, 571 (2015); https://doi.org/10.1186/s40064-015-1352-5
S.A. Amin and S. Gayen, J. Taibah Univ. Sci., 10, 896 (2016); https://doi.org/10.1016/j.jtusci.2016.04.009
I. Shahzadi, A.F. Zahoor, A. Rasul, A. Mansha, S. Ahmad and Z. Raza, ACS Omega, 6, 11943 (2021); https://doi.org/10.1021/acsomega.1c00424
R. Anitha, E. Kumar and S.C. Vella Durai, Asian J. Chem., 31, 1158 (2019); https://doi.org/10.14233/ajchem.2019.21910
E.S. Scott, E.E. Zeller and L.F. Audrieth, J. Org. Chem., 19, 749 (1954); https://doi.org/10.1021/jo01370a008
N. Bhagyalakshmi, R.H. Udupi and M.S. Niranjan, Int. J. Pharm. Chem. Sci., 1, 287 (2012).
A. Venkanna, B. Siva, B. Poornima, P.R. Rao Vadaparthi, K.R. Prasad, K.A. Reddy, G.B.P. Reddy and K.S. Babu, Fitoterapia, 95, 102 (2014); https://doi.org/10.1016/j.fitote.2014.03.003
O.O. Oyedapo and A.J. Famurewa, Int. J. Pharmacol., 33, 65 (1995).
N.I. Osman, N.J. Sidik, A. Awal, N.A. Adam and N.I. Rezali, J. Intercult. Ethnopharmacol., 5, 343 (2016); https://doi.org/10.5455/jice.20160731025522
A. Aline, M. Michel and L. Margareth, Med. Chem., 4, 517 (2014); https://doi.org/10.4172/2161-0444.1000188
N. Sreejayan and M. Rao, J. Pharm. Pharmacol., 49, 105 (1997); https://doi.org/10.1111/j.2042-7158.1997.tb06761.x
R. Re, N. Pellegrini, A. Proteggente, A. Pannala, M. Yang and C. RiceEvans, Free Radic. Biol. Med., 26, 1231 (1999); https://doi.org/10.1016/S0891-5849(98)00315-3
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C.H. Yap, Comput. Chem., 32, 1466 (2011); https://doi.org/10.1002/jcc.21707
https://dtclab.webs.com/software-tools
K. Roy, S. Kar and P. Ambure, Chemom. Intell. Lab. Syst., 145, 22 (2015); https://doi.org/10.1016/j.chemolab.2015.04.013
D. Kumudha, J.T. Leonard, M. Muthumani, N. Chidhambaranathan and T. Kalavathi, Asian J. Pharm. Clin. Res., 6, 5 (2013).
P.K. Goyal, A. Bhandari, A.C. Rana and D.S. Bele, Asian. J. Res. Chem., 3, 355 (2010).
R. Nilakantan, D.S. Nunn, L. Greenblatt, G. Walker, K. Haraki and D. Mobilio, J. Chem. Inform. Model, 46, 1069 (2006); https://doi.org/10.1021/ci050521b