Design of potent fluoro-substituted chalcones as antimicrobial agents

Abstract

Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9–15, and 20–23) using a structure–activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and three common fungal strains. Three derivatives (3, 9, and 10) displayed significant antitubercular activity with IC50 values of ≤16,760. Compounds derived from trimethoxy substituent scaffolds with monofluoro substitution on the B ring of the chalcone structure exhibited superior inhibition activity compared to corresponding hydroxy analogs. In terms of antimicrobial activity, most compounds (3, 9, 12–14, and 23) exhibited moderate to potent activity against the bacteria, and the antifungal activities of compounds 3, 13, 15, 20, and 22 were comparable to those of reference drugs ampicillin and fluconazole.

Synthesis, Characterization and Antibacterial Activities of New Fluorinated Chalcones

“…The research further revealed that fluorinated chalcones with fluoro-substitution in position 2 and or position 5 of its B ring showed higher antibacterial potency against S. aureus, S. pyogenes, E. feacalis, E. coli, P. aeruginosa and antifungal activity against C. albicans, C. glabrata and C. parapsilosis. However, the presence of hydroxyl group on the A ring decreases the antitubercular activity of theses fluorinated chalcones [18]. Also, fluorinated chalcones-1,2,3-triazoles conjugates have been reported to show significant activity against some bacterial and fungal strains [19].…”

Recent Advances in Chalcones: Synthesis, Transformation and Pharmacological Activities

“…In their paper, Thasneem and co-workers concluded that chalcone 91 with NH 2 and NO 2 showed excellent activity against Staphylococcus aureus (ATCC5922) and Escherichia coli (ATCC6633) respectively whereas OH showed excellent activity against Saccharomyces cerevisiae [33]. In another paper, compounds 92 with substituents H, 2-F, and 2,5-diF displayed activities against the S. aureus, S. pyogenes, E. faecalis, E. coli, and P. aeruginosa while 92 substituent H and compound 93 were active against tested C. albicans [34]. The presence of halogens in chalcone 94 increases microbial susceptibility [35].…”

“…Alam et al evaluated heterocyclic chalcones 101 for anti-tubercular activity [37], while, Solankee and Tailor found chalcone 102 to exhibit promising activity [38], In another work, compound 103 with trimethoxy on ring A and fluoro groups on the B showed enhance activity with IC 50 (≤16,760) against Mycobacterium tuberculosis H37Rv compared to the standard drugs Ethambutol (EMB) and Isoniazid (INH) [34] ( Fig. 7).…”

“…Chalcones are multifunctional molecules that possess promising pharmacological activities. Chalcones have been found useful as anticancer [23][24][25], antioxidant [26][27][28][29], antiinflammatory [30][31][32], anti-microbial [23,[33][34][35][36], anti-tubercular [34,37,38], antileishmanial [39], antimalarial [40][41][42], anthelmintic [27], osteogenic activity [43]. This review article focuses on recent applications of Claisen-Schmidt condensation reaction employed in the synthesis of chalcone, its transformation to heterocyclic compounds and pharmacological activities.…”

Biological Role of Chalcones in Medicinal Chemistry

“…Burmaoglu et al reported antimicrobial activity of fluoro-substituted chalcones (8) and (9) against S. aureus, S. pyogenes, E. faecalis, E. coli, and P. aeruginosa bacteria and C. albicans, C. glabrata, and C. parapsilosis fungal strains. Some of the tested compounds also exhibited antitubercular activity against Mycobacterium tuberculosis [13].…”