Monocarbonyl Curcumin-Based Molecular Hybrids as Potent Antibacterial Agents

Abstract

Keeping in view various pharmacological attributes of curcumin, coumarin, and isatin derivatives, triazole-tethered monocarbonyl curcumin-coumarin and curcumin-isatin molecular hybrids have been synthesized and evaluated for their antibacterial potential against Gram-positive (<i>Enterococcus faecalis</i> and <i>Staphylococcus aureus</i>) and Gram-negative (<i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i>) human pathogenic bacterial strains. Among all hybrid molecules, <b>A-4</b> and <b>B-38</b> showed the most potent antibacterial activity with inhibition zones of 29 and 31 mm along with MIC values of 12.50 and 6.25 μg/mL, respectively. Structure-activity relationship that emerged from biological data revealed that the two-carbon alkyl chain between triazole and coumarin/isatin moiety is well tolerable for the activity. Bromo substitution at the fifth position of isatin, para-cholo substitution in the case of curcumin-isatin, and para-methoxy in the case of curcumin-coumarin hybrids on ring A of curcumin are most suitable groups for the antibacterial activity. Various types of binding interactions of <b>A-4</b> and <b>B-38</b> within the active site of dihydrofolate reductase (DHFR) of <i>S. aureus</i> are also streamlined by molecular modeling studies, suggesting their capability in completely blocking DHFR.