Synthesis, molecular modelling and antibacterial activity of 4-aryl-thiosemicarbazides

• Autorzy: Bhat Mashooq Ahmad , Naglah Ahmad M. , Khan Azmat Ali , Al-Dhfyan Abdullah

Identyfikatory

DOI

10.2478/pjct-2022-0006

• Języki publikacji: EN

Abstrakty

EN

N-Substituted phenyl/cyclohexyl-2-(pyridine-4-carbonyl) hydrazine-1-carbothioamides (2a–r) were synthesized, characterized by spectral and analytical data. The compounds were evaluated for antibacterial activity by the discdiffusion method. Most of the compounds showed activity against Gram-positive bacteria. Compound 2h with 4-Sulfapyrimidine phenyl substitution was found to be the most promising candidate, active against Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) of (2–7 μg/mL). From the docking study, we predicted that compounds (2r, 2g, 2h, 2o, 2p and 2e) possess better antibacterial activity by having a good binding affinity with target protein and they could be used as potential drugs as antimicrobials. Amongst all the docked compounds, the compound 2h presented near binding affinity & interaction docking score with DNA gyrase enzymes with reference to ciprofoxacin.

Słowa kluczowe

EN

Aryl-thiosemicarbazides; antibacterial activity; molecular docking; DNAGyrase

• Wydawca: West Pomeranian University of Technology. Publishing House
• Czasopismo: Polish Journal of Chemical Technology
• Rocznik: 2022
• Tom: Vol. 24, nr 1
• Strony: 39--46
• Opis fizyczny: Bibliogr. 32 poz., rys., tab., wz.

Twórcy

autor

Bhat Mashooq Ahmad

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Naglah Ahmad M.

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Khan Azmat Ali

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Al-Dhfyan Abdullah

• Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Bibliografia

• 1. Breijyeh, Z., Jubeh, B. & Karaman, R. (2020). Resistance of Gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules. 25, 1340. DOI: 10.3390/molecules25061340.
• 2. Hiasa, H. (2018). DNA Topoisomerases as Targets for Antibacterial Agents. Methods Mol. Biol. 1703, 47–62. DOI: 10.1007/978-1-4939-7459-7_3.
• 3. Alt, S., Mitchenall, L.A., Maxwell, A. & Heide, L. (2011). Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics. J. Antimicrob. Chemother. 66, 2061–2069. DOI: 10.1093/jac/dkr247.
• 4. Pham, T.D.M., Ziora, Z.M. & Blaskovich, M.A.T. (2019). Quinolone antibiotics. Medchemcomm. 10, 1719––1739. DOI: 10.1039/c9md00120d.
• 5. Jalilian, A.R., Sattari, S., Bineshmarvasti, M., Daneshtalab, M. & Shafiee, A.R. (2003). Synthesis and in vitro antifungal and cytotoxicity evaluation of substituted 4,5-dihydronaphtho[1,2- d][1,2,3]thia(or selena)diazoles. IL Farmaco 58, 63−68.
• 6. Siwek, S.J., Dzitko, K. & Ruszezak, A. (2012). Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives. J. Mol. Model. 18, 4159−4170.
• 7. Gopalakrishnan, M., Sureshkumar, P., Thanusu, J. & Kanagarajan, V. (2008). Unusual formation of N-hydroxy-3,3--dimethyl-2,6-diarylpiperidin-4-one and its thiosemicarbazide derivative -synthesis and antimicrobial activity. Pharm. Chem. J. 42, 271−276.
• 8. Siddiqui, N. & Singh, O. (2003). Antibacterial activity of some 4-Nsubstituted thiosemicarbazides and thiosemicarbazones. Indian J. Pharm. Sci. 65, 423−425.
• 9. Plech, T., Wujec, M., Siwek, A., Kosikowska, U. & Malm, A. (2011). Synthesis and antimicrobial activity of thiosemicarbazides, s-triazoles and their Mannich bases bearing 3-chlorophenyl moiety. Eur. J. Med. Chem. 46, 241–248.
• 10. Sheikhy, M., Jalilian, A.R., Novinrooz, A. & Motamedi-Sedeh, F. (2012). Synthesis and in vitro antibacterial evaluation of some thiosemicarbazides and thiosemicarbazones. J. Biomed. Sci. Eng. 5, 39−42.
• 11. Umadevi, P., Deepti, K., Srinath, I., Vijayalakshmi, G. & Tarakaramji, M. (2012). Synthesis and in-vitro antibacterial activity of some new urea, thiourea and thiosemicarbazide derivatives. Int. J. Pharm. Pharm. Sci. 4, 379−383.
• 12. Haraguchi, S.K., Silva, A.A., Vidotti, G.J., Dos, V., Santos, P., Garcia, F.P. & Pedroso, R.B. (2011). Antitrypanosomal activity of novel benzaldehyde-thiosemicarbazone derivatives from Kaurenoic acid. Molecules 16, 1166−1180.
• 13. Leite, A.C.L., de Lima, R.S., Moreira, D.R. de M., Cardoso, M.V., de Brito, A. & Santos, L.M.F. (2006). Synthesis, docking and in vitro activity of thiosemicarbazones, aminoacylthiosemicarbazides and acyl-thiazolidones against Trypanosoma cruzi. Bioorg. Med. Chem. 14, 3749−3757.
• 14. Chipeleme, G.J., Rosenthal, B.P.J. & Chibale, K. (2007). Design, synthesis, and antimalarial activity of structural chimeras of thiosemicarbazone and ferroquine analogues. Bioorg. Med. Chem. 17, 6434−6438.
• 15. Klayman, D.L., Scovill, J.P., Bartosevich, J.F. & Bruce, J. (1983). 2-Acetylpyridine thiosemicarbazones.1-[l-(2-Pyridyl) ethyl]-3-thiosemicarbazides as potential antimalarial agents. J. Med. Chem. 26, 35−39.
• 16. Zhang, H.J., Qian, Y., Zhu, D.D., Yang, X.G. & Zhu, H.L. (2011). Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents. Eur. J. Med. Chem. 46, 4702−4708.
• 17. Rastogi, S. & Rastogi, H. (2010). An efficient synthesis of some substituted piperidin-4-one thiosemicarbazone derivatives as potential anticonvulsant under microwave irradiation. Indian J. Chem. 49, 547−553.
• 18. Soliman, R., Gabr, M., Abouzeit-har, M.S. & Sharabi, F.M. (1981). Formation of thiazoles, thiazines and thiadiazines from 1-phthalazine thiosemicarbazides as potential anticonvulsants. J. Pharm. Sci. 70, 94−96.
• 19. Cardiaa, M.C., Distinto, S., Maccioni, E., Plumitallo, A., Saddi, M. & Sanna, M.L. (2006). Isonicotinoylhydrazothiazoles and isonicotinoyl-N4-substituted thiosemicarbazides: synthesis, characterization, and anti-mycobacterial activity. J. Hetero. Chem. 43, 1337−1342.
• 20. Siwek, A., Staczek, P., Wujec, M., Bielawski, K., Bielawska, A. & Paneth, P. (2013). Cytotoxic effect and molecular docking of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide a novel topoisomerase II inhibitor. J. Mol. Model. 19, 1319−1324.
• 21. Siwek, A., Staczek, P., Wujec, M., Stefànska, J., Kosikowska, U., Malm, A., Jankowoski, S. & Paneth, P. (2011). Biological and docking studies of topoisomerase IV inhibition by thiosemicarbazides. J. Mol. Model. 17, 2297–2303. DOI:10.1007/s00894-010-0889-z.
• 22. Banerjee, D., Yogeeswari, P., Bhat, P., Thomas, A., Srividya, M. & Shriram, D. (2011). Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV-TB coinfection. Eur. J. Med. Chem. 46, 106−121. DOI:10.1016/j. ejmech.2010.10.020.
• 23. Paneth, A., Stączek, P., Plech, T., Strzelczyk, A., Dzitko, K., Wujec, M., Kuśmierz, E., Kosikowska, U., Grzegorczyk, A. & Paneth, P. (2016). Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors. J. Enzyme Inhib. Med. Chem. 31, 14−22. DOI:10.3109/14756366.2014.1003214.
• 24. Siwek, A., Stączek, P. & Stefańska, J. (2011) Synthesis and structure-activity relationship studies of 4-arylthiosemicarbazides as topoisomerase IV inhibitors with Gram-positive antibacterial activity. Search for molecular basis of antibacterial activity of thiosemicarbazides. Eur. J. Med. Chem. 46, 5717−5726.
• 25. Packiarajan, M., Coate, H., Desai, M., Jimenez, H.N., Reinhard, E.J., Jubian, V.J., Marzabadi, M.R., Chandrasena, G., Wolinski, T.C., Walker, M.W. & Andersen, K. (2011). 5-(2’-Pyridyl)-2-aminothiazoles: alkyl amino sulfonamides and sulfamides as potent NPY(5) antagonists. Bioorg. Med. Chem. Lett. 21, 6500–6504. DOI: 10.1016/j.bmcl.2011.08.072.
• 26. Duan, M., Kazmierski, W.M., Chong, P.Y., Deanda, F., Edelstein, M., Ferris, R., Peckham, J., Wheelan, P., Xiong, Z., Zhang, H., Nishizawa, R. & Takaoka, Y. (2011). Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats. Bioorg. Med. Chem. Lett. 21, 6470–6475. DOI: 10.1016/j. bmcl.2011.08.080.
• 27. Luedtke, G.R., Schinzel, K., Tan, X., Tester, R.W., Nashashibi, I., Xu, Y.J., Dugar, S., Levy, D.E. & Jung, J. (2101). Amide-based inhibitors of p38 alpha MAP kinase. Part 1: discovery of novel N-pyridyl amide lead molecules. Bioorg. Med. Chem. Lett. 20, 2556−2559.
• 28. De Beer, E.J. & Sherwood, M.B. (1945). The Paper-Disc Agar-Plate Method for the Assay of Antibiotic Substances. J. Bacteriol. 50, 459−67.
• 29. Williams, S.T. & Cross, T. Actinomycetes. In: Booth, C., Ed., Methods in Microbiology, 1971, Academic Press, London, 295.
• 30. Trott, O. & Olson, A.J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455−461.
• 31. Bhat, M.A., Khan, A.A., Ghabbour, H., Quah, C.K. & Fun, H.K. (2016). Synthesis, characterization, x-ray structure and antimicrobial activity of N-(4-chlorophenyl)-2-(pyridin--4-ylcarbonyl) hydrazinecarbothioamide. Tropical J. Pharm. Res. 15, 1751–1757. DOI: 10.4314/tjpr.v15i8.22.
• 32. Bhat, M.A., Khan, A.A., Khan, S., Al-Omar, M.A. & Parvez, M.K. (2014). Synthesis and anti-Candidal activity of N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide. Bioorg. Med. Chem. Lett. 24, 1299–1302. DOI: 10.1016/j.bmcl.2014.01.060.

Uwagi

Opracowanie rekordu ze środków MEiN, umowa nr SONP/SP/546092/2022 w ramach programu "Społeczna odpowiedzialność nauki" - moduł: Popularyzacja nauki i promocja sportu (2022-2023).