Issue

Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Copyright (c) 2024 Monika Saini, Dinesh Kumar Mehta, Kumar Guarve, Manjinder Singh, Rina Das

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Design, Synthesis and Biological Evaluation of 4,6-Substituted 2-Styrylquinoline Derivatives: Potential Antimicrobial and Anticancer Agents

https://doi.org/10.14233/ajchem.2024.32775
Monika Saini
Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-133207, India
https://orcid.org/0009-0004-9421-9042
Dinesh Kumar Mehta
Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-133207, India
https://orcid.org/0000-0003-4908-7437
Kumar Guarve
Guru Gobind Singh College of Pharmacy, Yamunanagar-135001, India
https://orcid.org/0000-0002-7066-3438
Manjinder Singh
Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0000-0001-5477-9222
Rina Das
Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-133207, India
https://orcid.org/0000-0002-2535-2729

Corresponding Author(s) : Dinesh Kumar Mehta

dkmehta17@rediffmail.com

Asian Journal of Chemistry, Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Abstract

A series of novel 4,6-substituted 2-styrylquinoline derivatives (3a-h) was designed and synthesized based on the substitution in quinoline scaffolds (with Br, H, NO2 at C6 position) as well as the substitution in the styryl moeity (at C4' position). The target compounds were investigated for their antimicrobial activity against Gram-positive Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212) and Gram-negative bacterium Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC 10231) and anticancer activity against human colon adenocarcinoma HT29 cells. Compared to standard drug ciprofloxacin, compounds 3e, 3b and 3c showed significant antibacterial activity against Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Additionally, synthesized compound 3e had significant activity against Candida albicans with MIC value of 8 µg/mL. In anticancer study, the maximum cell death rate was found in compounds 3e, 3b and 3c at the dose of 100 µM i.e., 72.9%., 44.01% and 35.46%, respectively and the measured IC50 were 58.84, 114.53 and 130 µM. The cytotoxic potential of compound 3e was confirmed by AO-EtBr dual staining assay in which red fluorescence of necrotic cells lost their membrane integrity due to toxicity induced by compound 3e. This growth inhibition and apoptotic activity of compound 3e was dose-dependent when the colour changed from green to red. Furthermore, in silico studies were conducted on the synthesized compounds to elucidate the potential mechanisms of action against dihydrofolate reductase (DHFR) from E. coli, DNA gyrase from P. aeruginosa, DHFR from S. aureus, acetolactate synthase from K. pneumoniae and DHFR from C. albicans. The derivatives also exhibited the strongest ligand-receptor binding affinity. Additionally, ADME analysis was performed to predict the pharmacokinetic profiles of the compounds, indicating good oral drug-like properties.

Keywords

Antimicrobial Anticancer In silico studies 2-Styrylquinolines Pfitzinger reaction Molecular docking
Saini, M., Mehta, D. K., Guarve, K., Singh, M., & Das, R. (2024). Design, Synthesis and Biological Evaluation of 4,6-Substituted 2-Styrylquinoline Derivatives: Potential Antimicrobial and Anticancer Agents. Asian Journal of Chemistry, 36(12), 2951–2960. https://doi.org/10.14233/ajchem.2024.32775
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. C.A. Michael, D. Dominey-Howes and M. Labbate, Front. Public Health, 2, 145 (2014); https://doi.org/10.3389/fpubh.2014.00145
  2. R.J. Fair and Y. Tor, Perspect. Med. Chem., 6, 14459 (2014); https://doi.org/10.4137/PMC.S14459
  3. V. Economou and P. Gousia, Infect. Drug Resist., 2015, 49 (2015); https://doi.org/10.2147/IDR.S55778
  4. E. Christaki, M. Marcou and A. Tofarides, J. Mol. Evol., 88, 26 (2020); https://doi.org/10.1007/s00239-019-09914-3
  5. T. Krell and M.A. Matilla, Microb. Biotechnol., 15, 70 (2022); https://doi.org/10.1111/1751-7915.13945
  6. J. Polanski, H. Niedbala, R. Musiol, D. Tabak, B. Podeszwa, A. Bak, R. Gieleciak, A. Palka and T. Magdziarz, Acta Poloniae Pharm. Drug Res., 61, 3 (2004).
  7. V. Sharma, D. Kumar Mehta and R. Das, Mini Rev. Med. Chem., 17, 1557 (2017); https://doi.org/10.2174/1389557517666170510104954
  8. M. Özyanik, S. Demirci, H. Bektas, N. Demirbas, A. Demirbas and S.A. Karaoglu, Turk. J. Chem., 36, 233 (2012).
  9. W. Cieslik, R. Musiol, J.E. Nycz, J. Jampilek, M. Vejsova, M. Wolff, B. Machura and J. Polanski, Bioorg. Med. Chem., 20, 6960 (2012); https://doi.org/10.1016/j.bmc.2012.10.027
  10. S. Vandekerckhove, S. De Moor, D. Segers, C. de Kock, P.J. Smith, K. Chibale, N. De Kimpe and M. D’hooghe, MedChemComm, 4, 724 (2013); https://doi.org/10.1039/c3md20377h
  11. H.R. Bhat, U.P. Singh, P. Gahtori, S.K. Ghosh, K. Gogoi, A. Prakash and R.K. Singh, New J. Chem., 37, 2654 (2013); https://doi.org/10.1039/c3nj00317e
  12. B.F. Roberts, Y. Zheng, J. Cleaveleand, S. Lee, E. Lee, L. Ayong, Y. Yuan and D. Chakrabarti, Int. J. Parasitol. Drugs Drug Resist., 7, 120 (2017); https://doi.org/10.1016/j.ijpddr.2017.02.002
  13. X.-Q. Wang, C.L. Xia, S.B. Chen, J.H. Tan, T.M. Ou, S.L. Huang, D. Li, L.Q. Gu and Z.S. Huang, Eur. J. Med. Chem., 89, 349 (2015); https://doi.org/10.1016/j.ejmech.2014.10.018
  14. A. Luczywo, I.P. Sauter, T.C. da Silva Ferreira, M. Cortez, G.P. Romanelli, G. Sathicq and S.E. Asís, J. Heterocycl. Chem., 58, 822 (2021); https://doi.org/10.1002/jhet.4217
  15. L.G. de Araújo, A.A. De Jesus, J.R. Dantas, L.E. de Oliveira, B.G. Vaz, G.F. dos Santos, C.M. Cristiano, C.G. Lima-Junior, V.J. de Oliveira, K.C. Weber, E.G. Barbosa et al., Dyes Pigments, 11, 2294 (2024).
  16. R. Musiol, Med. Chem., 16, 141 (2020); https://doi.org/10.2174/1573406415666190603103012
  17. M. Baghbanzadeh, L. Carbone, P.D. Cozzoli and C.O. Kappe, Angew. Chem. Int. Ed., 50, 11312 (2011); https://doi.org/10.1002/anie.201101274
  18. D. Kaleeswaran and R. Murugavel, J. Chem. Sci., 130, 1 (2018); https://doi.org/10.1007/s12039-017-1403-2
  19. A. Gaurav and R. Singh, Med. Chem. Res., 23, 5008 (2014); https://doi.org/10.1007/s00044-014-1048-3
  20. R. Musiol, J. Jampilek, J.E. Nycz, M. Pesko, J. Carroll, K. Kralova, M. Vejsova, J. O’Mahony, A. Coffey, A. Mrozek and J. Polanski, Molecules, 15, 288 (2010); https://doi.org/10.3390/molecules15010288
  21. R. Musiol, M. Serda, S. Hensel-Bielowka and J. Polanski, Curr. Med. Chem., 17, 1960 (2010); https://doi.org/10.2174/092986710791163966
  22. Y. Li, X. Shi, N. Xie, Y. Zhao and S. Li, MedChemComm, 4, 367 (2013); https://doi.org/10.1039/C2MD20275A
  23. M. Dhanawat, D.K. Mehta and R. Das, Mini Rev. Med. Chem., 21, 1849 (2021); https://doi.org/10.2174/1389557521666210225115055
  24. A. Dubrovin, A.I. Mikhalev, S.V. Ukhov, A.G. Goldshtein, V.V. Novikova, T.F. Odegova and R.R. Makhmudov, Pharm. Chem. J., 49, 309 (2015); https://doi.org/10.1007/s11094-015-1275-z
  25. S. Zarougui, M. Er-rajy, A. Faris, H. Imtara, M. El fadili, O. Al kamaly, S. Zuhair Alshawwa, F.A. Nasr, M. Aloui and M. Elhallaoui, J. Saudi Chem. Soc., 27, 101728 (2023); https://doi.org/10.1016/j.jscs.2023.101728
  26. V. Sharma, R. Das, D.K. Mehta, D. Sharma and R.K. Sahu, Mini Rev. Med. Chem., 22, 69 (2022); https://doi.org/10.2174/1389557521666210112142136
  27. M. Saini, R. Das, D.K. Mehta and S. Chauhan, Med. Chem., 18, 859 (2022); https://doi.org/10.2174/1573406418666220214085856
  28. V. Sharma, R. Das, D.K. Mehta, D. Sharma, S. Aman and M.U. Khan, Mol. Divers., 1 (2024); https://doi.org/10.1007/s11030-024-10862-4
  29. H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov and P.E. Bourne, Nucleic Acids Res., 28, 235 (2000); https://doi.org/10.1093/nar/28.1.235
  30. I. Khan, K.R. Garikapati, A. Setti, A.B. Shaik, V.K. Kanth Makani, M.A. Shareef, H. Rajpurohit, N. Vangara, M. Pal-Bhadra, A. Kamal and C.G. Kumar, Eur. J. Med. Chem., 163, 636 (2019); https://doi.org/10.1016/j.ejmech.2018.12.011
  31. D. Ranjith and C. Ravikumar, J. Pharmacogn. Phytochem., 8, 2063 (2019).
  32. M.H. Rezadoost, H.H. Kumleh and A. Ghasempour, Mol. Biol. Rep., 46, 5131 (2019); https://doi.org/10.1007/s11033-019-04970-w
  33. S. Das, A. Rahaman, R. Nath, A. Das Talukdar, D. Nath, S. Bhattacharjee, D.P. Mandal, M.D. Choudhury, D. Das, G. Das and J.K. Patra, J. Ethnopharmacol., 300, 115729 (2023); https://doi.org/10.1016/j.jep.2022.115729
  34. P. Das, T. Dutta, S. Manna, S. Loganathan and P. Basak, Environ. Res., 204, 111962 (2022); https://doi.org/10.1016/j.envres.2021.111962
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 0 Download : 0