Copyright (c) 2024 T.Sudha Thomas, Lakshmi, sivan
This work is licensed under a Creative Commons Attribution 4.0 International License.
Design, Synthesis, Characterization, Molecular Docking Studies, In vitro and In vivo Cervical Cancer Activity of Novel N-Substituted Pyrazole Derivatives
Corresponding Author(s) : P. Kumar Nallasivan
Asian Journal of Chemistry,
Vol. 36 No. 10 (2024): Vol 36 Issue 10, 2024
Abstract
The aim of this study is to design, synthesize, characterize few novel N-substituted pyrazole derivatives and evaluated for their anticancer capabilities; these compounds were selected based on their ability to inhibit the HPV E6 protein. The IR, 1H & 13C NMR, mass spectral and elemental analysis were used to determine the structural details of the newly synthesized substances. The molecular docking was performed using Auto Dock Vina, and the protein-ligand interaction was analyzed using Discovery Studio. The sulforhodamine B (SRB) assay was used to determine the in vitro anticancer activity against the HeLa cell line. Body weight analysis, mean survival time and % increase in life span approaches were used to assess in vivo anticancer effectiveness in Swiss albino mice bearing Dalton’s Lymphoma Ascites (DAL) tumor model. Synthesized compounds have excellent docking energies, according to docking experiments. Compounds I, II and III were selected for anticancer activity in vivo DAL-bearing mice based on the findings of their in vitro and SRB assays exhibiting the antiproliferative activity. Pyrazole derivatives, compounds I and III, demonstrated significant potential as anticancer agents.
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- U.T. Sankpal, H. Pius, M. Khan, M.I. Shukoor, P. Maliakal, C.M. Lee, M. Abdelrahim, S.F. Connelly and R. Basha, Tumour Biol., 33, 1265 (2012); https://doi.org/10.1007/s13277-012-0413-4
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- M.P. Sathisha, V.K. Revankar and K.S.R. Pai, Met. Based Drugs, 2008, 362105 (2008); https://doi.org/10.1155/2008/362105
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References
U.T. Sankpal, H. Pius, M. Khan, M.I. Shukoor, P. Maliakal, C.M. Lee, M. Abdelrahim, S.F. Connelly and R. Basha, Tumour Biol., 33, 1265 (2012); https://doi.org/10.1007/s13277-012-0413-4
S. Adel, E. Azab, A. Mohamed, A. Omar, A.M. Alaa, I. Naglaa et al., Eur. J. Med. Chem., 45, 9 (2010).
Y. Gao, K.J. Shen, L. Milane, J. Hornicek, M. Amiji and Z. Duan, Curr. Med. Chem., 22, 1335 (2015); https://doi.org/10.2174/0929867322666150209151851
T. Brzozowski, Curr. Med. Chem., 19, 2 (2012); https://doi.org/10.2174/092986712803414024
S.T. Al-Rashood, I.A. Aboldahab, M.N. Nagi, L.A. Abouzeid, A.A.M. Abdel-Aziz, S.G. Abdel-hamide, K.M. Youssef, A.M. Al-Obaid and H.I. El-Subbagh, Bioorg. Med. Chem., 14, 24 (2006); https://doi.org/10.1016/j.bmc.2006.08.030
F. Sams-Dodd, Drug Discov. Today, 18, 211 (2013); https://doi.org/10.1016/j.drudis.2012.10.010
X. Sun, S. Vilar and N.P. Tatonetti, Sci. Transl. Med., 5, 205 (2013); https://doi.org/10.1126/scitranslmed.3006667
P.N. Dube, S.S. Bule, S.N. Mokale, M.R. Kumbhare, P.R. Dighe and Y.V. Ushir, Chem. Biol. Drug Des., 84, 409 (2014); https://doi.org/10.1111/cbdd.12324
B. Maggio, D. Raffa, M.V. Raimondi, F. Plescia, M.L. Trincavelli, C. Martini, F. Meneghetti, L. Basile, S. Guccione and G. Daidone, Eur. J. Med. Chem., 54, 709 (2012); https://doi.org/10.1016/j.ejmech.2012.06.028
A. Ahmad, H. Varshney, A. Rauf, F.M. Husain and I. Ahmad, J. King Saud Univ. Sci., 26, 290 (2014); https://doi.org/10.1016/j.jksus.2013.09.003
N. Das, A. Verma, P.K. Shrivastava and S.K. Shrivastava, Indian J. Chem., 47B, 1555 (2008).
E.K. Yim and J.S. Park, Cancer Res. Treat., 37, 319 (2005); https://doi.org/10.4143/crt.2005.37.6.319
P.N. Dube, S.S. Bule, Y.V. Ushir, M.R. Kumbhare and P.R. Dighe, Med. Chem. Res., 24, 1070 (2015); https://doi.org/10.1007/s00044-014-1201-z
N.V. Patel and D.J. Sen, Am. J. Adv. Drug Deliv., 1, 2 (2013).
A. Garofalo, L. Goossens, P. Six, A. Lemoine, S. Ravez, A. Farce and P. Depreux, Bioorg. Med. Chem. Lett., 21, 2106 (2011); https://doi.org/10.1016/j.bmcl.2011.01.137
P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. Warren, H. Bokesch, S. Kenney and M.R. Boyd, J. Natl. Cancer Inst., 82, 1107 (1990); https://doi.org/10.1093/jnci/82.13.1107
A. Monks, D. Scudiero, P. Skehan, R. Shoemaker, K. Paull, D. Vistica, C. Hose, J. Langley, P. Cronise, A. Vaigro-Wolff, M. Gray-Goodrich, H. Campbell, J. Mayo and M. Boyd, J. Natl. Cancer Inst., 83, 757 (1991); https://doi.org/10.1093/jnci/83.11.757
A.E. Eckhardt, B.N. Malone and I.J. Goldstein, Cancer Res., 42, 2977 (1982).
M.P. Sathisha, V.K. Revankar and K.S.R. Pai, Met. Based Drugs, 2008, 362105 (2008); https://doi.org/10.1155/2008/362105
A. Mukherjee, S. Dutta and U. Sanyal, J. Exp. Clin. Cancer Res., 26, 489 (2007).
S. Kameshwaran, V. Suresh, G. Arunachalam, S.K. Kanthlal, M. Mohanraj, Int. Res. J. Pharm., 3, 246 (2012).