Novel coumarin linked pyrazoles, thiazoles, and thiadiazoles: synthetic strategies and in vitro antimicrobial investigation

Abstract

Aim: Emerging resistance among pathogens necessitates the development of novel antimicrobial agents. As a result, we aimed to synthesize new coumarins and study their antimicrobial activity with the hope of obtaining effective drugs.

Method: A series of coumarins were synthesized, characterized, and assessed for antimicrobial activity using broth microdilution and agar diffusion methods against Gram-positive (Bacillus pumilis, Streptococcus faecalis), Gram-negative (Escherichia coli, Enterobacter cloacae) bacteria, and fungi (Saccharomyces cerevisiae, Candida albicans).

Results: Pyrazoles 15 and 16 revealed promising activities against all bacterial strains with MIC values ranging from 1.95 to 15.6 µg/ml. Notably, pyrazole 15 with CF₃ in 3-position of pyrazole ring demonstrated higher ability to inhibit Streptococcus faecalis strain with MIC value equal to penicillin G (3.91 µg/ml). It also exhibited the best bactericidal potency against Escherichia coli with MBC value of 15.6 µg/ml while, pyrazole 16 recorded the same MBC value against Enterobacter cloacae. Pyrazole 15 demonstrated the strongest antifungal activity against both fungal strains with MIC and MFC values of 15.6, 7.81, 62.5, and 31.3 µg/ml against Saccharomyces cerevisiae and Candida albicans, respectively.

Conclusion: These findings underscore the potential of coumarins, particularly compounds 15 and 16, as effective antimicrobial agents and provide critical insights into the design of bioactive molecules.

Keywords: 1,3-thiazoles, 1.3.4-thiadiazines; Coumarins; antimicrobial activity; pyrazoles.