Design, synthesis, and molecular docking of cysteine-based sulphonamide derivatives as antimicrobial agents.

Autor: Egbujor MC; Department of Industrial Chemistry, Renaissance University, Ugbawka, Enugu State, Nigeria., Okoro UC; Synthetic Organic Chemistry Division, Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Enugu State, Nigeria., Okafor SN; Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Enugu State, Nigeria., Egu SA; Department of Pure and Industrial Chemistry, Kogi State University, Anyigba, Kogi State, Nigeria., Amasiatu IS; Department of Biochemistry, Renaissance University, Ugbawka, Enugu State, Nigeria., Egwuatu PI; Department of Microbiology, Renaissance University, Ugbawka, Enugu State, Nigeria., Umeh OR; Department of Applied Microbiology and Brewing, Nnamdi Azikiwe University, P.M.B 5025 Awka, Anambra State, Nigeria., Ibo EM; Department of Applied Microbiology and Brewing, Nnamdi Azikiwe University, P.M.B 5025 Awka, Anambra State, Nigeria.
Jazyk: angličtina
Zdroj: Research in pharmaceutical sciences [Res Pharm Sci] 2021 Nov 11; Vol. 17 (1), pp. 99-110. Date of Electronic Publication: 2021 Nov 11 (Print Publication: 2022).
DOI: 10.4103/1735-5362.329930
Abstrakt: Background and Purpose: The preponderance of microbial infections remains a global challenge. In the present study, synthesis of novel cysteine-based antimicrobial agents and their biological evaluation is reported.
Experimental Approach: The reaction of p -toluenesulphonyl chloride with cysteine afforded 2-{[(4-methylphenyl)sulphonyl]amino}-3-sulphanylpropanoic acid (3) which was acetylated based on Lumiere-Barbier method using acetic anhydride. The ammonolysis of the acetylated compound (4) gave the carboxamide derivative ( 5 ) which reacted with aniline, aminopyridine and diaminopyrimidine via nickel catalyzed Buchwald-Hartwig amidation reaction to afford compounds 6a, 6b, and 6c , respectively. The compounds were characterized using FTIR, 1 H-NMR, 13 C-NMR, and elemental analysis. The in vitro antimicrobial activities were determined. Their physicochemical properties were generated in silico and the molecular docking studied bacterial and fungal infections.
Findings/results: Compounds 4, 6b, and 6c exhibited excellent in vitro antibacterial activities while compound 4 had the best antifungal activities. From the in silico antimicrobial results, compound 3 had a better binding affinity (-10.95 kcal/mol) than penicillin (-10.89 kcal/mol) while compounds 3 and 4 had binding affinities (-10.07 and -10.62kcal/mol) comparable to ketoconazole (-10.85 kcal/mol).
Conclusion and Implication: All the synthesized compounds exhibited significant antibacterial and antifungal activities and were confirmed to be potential antimicrobial agents.
Competing Interests: The authors declared no conflicts of interest in this study.
(Copyright: © 2021 Research in Pharmaceutical Sciences.)
Databáze: MEDLINE
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