Structure-based drug discovery and antimicrobial activity of ciprofloxacin-grafted Ugi adducts

A new series of ciprofloxacin-derived Ugi adducts were rationally designed and synthesized. The synthesized molecules were explored for their potential antimicrobial activities against four pathogenic microorganisms. Among these derivatives, compound 7h with a 4-nitrophenyl substituent at R-2 exhibited significant activity against two tested Gram-positive bacteria with a minimum inhibitory concentration value of 0.097 mu g/mL while 7i bearing 4-chlorophenyl pendant demonstrated the best antimicrobial activities against Gram-negative bacteria. Furthermore, the analysis of the structure-activity relationships disclosed that types of substitutions differently affect the bacteria so the most potent derivative against Gram-negative infections was the least active one in Gram-positive microorganisms. Also, the molecular docking and molecular dynamic simulations were executed on 7i as the most potent Gram-negative anti-bacterial agent against ATP-binding sites of DNA gyrase B. Accordingly, our findings suggest that ciprofloxacin-based Ugi adducts are an interesting precursor for the design of potent antimicrobial agents. Communicated by Ramaswamy H. Sarma.

Automated summary

A series of ciprofloxacin-derived Ugi adducts were designed and synthesized, and their antimicrobial activities were evaluated. The study revealed that different substituents have varied effects on the antimicrobial activities against Gram-negative and Gram-positive bacteria. The most potent derivative against Gram-negative bacteria showed lower activity against Gram-positive microorganisms. Molecular docking and molecular dynamic simulations were performed, showing the binding of one derivative to the ATP-binding sites of DNA gyrase B.