Aryl-n-hexanamide linked enaminones of usnic acid as promising antimicrobial agents

Lichen secondary metabolites are well explored medicinal agents with diverse pharmacological properties. One of the important antibiotic lichen secondary metabolites is usnic acid. Its diverse medicinal profiles prompted us to explore it as a potential antitubercular molecule. Towards this direction, continuing our efforts on the discovery and development of new analogs with potent antitubercular properties we designed, synthesized, and evaluated a set of 37 usnic acid enaminonecoupled aryl-n-hexanamides (3-39). The study yielded a 3,4-dimethoxyphenyl compound (13, 5.3 mu M) as the most active anti-TB molecule. The docking studies were performed on 7 different enzymes to better understand the binding modes, where it was observed that compound 13 bound strongly with glucose dehydrogenase (Gscore: - 9.03). Further antibacterial investigations revealed compound 2 with potent inhibition on Salmonella typhi and Bacillus subtilis (MIC 3 mu M) and MIC values of 7 and 14 mu M on Streptococcus mutans and Escherichia coli respectively. Compound 19 (3-F-5-CF3-phenyl) displayed encouraging antibacterial profiles against E. coli, S. typhi and S. mutans with MIC values of 10 mu M respectively. Interestingly, compound 20 (2,6-difluorophenyl) also displayed good antibacterial activity against E. coli with an MIC value of 6 mu M. These encouraging pharmacological results will help for better designing and developing usnic acid-based semisynthetic derivatives as potential antimicrobial agents. [GRAPHICS] .

Automated summary

Lichen secondary metabolite usnic acid is a potential antitubercular and antibacterial molecule. Through designing, synthesizing, and evaluating a set of usnic acid derivatives, several compounds with potential antitubercular and antibacterial activity were discovered. These pharmacological results will contribute to the development of usnic acid derivatives as potential antimicrobial agents.