Structure-Based Drug Discovery and Antimicrobial Activity of Ciprofloxacin‐Grafted Ugi Adducts Publisher Pubmed



Tahmasebi B¹ ; Iraji A^{2, 3} ; Sherafati M⁴ ; Moazzam A⁴ ; Akhlagh SA⁵ ; Adib M¹ ; Mahdavi M⁴ Show Affiliations
Source: Journal of Biomolecular Structure and Dynamics Published:2023

Abstract

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 R2 exhibited significant activity against two tested Gram-positive bacteria with a minimum inhibitory concentration value of 0.097 µg/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. © 2022 Informa UK Limited, trading as Taylor & Francis Group.