Design, synthesis and docking studies of ciprofloxacin analogues as potential antimicrobial agents against resistant pathogens

Abstract

Antibiotic resistance is one of the leading fears worldwide. Development of resistance against antimicrobial agents is one of the major purposes for research and development of new molecules. Ciprofloxacin analogues have grounds continuous interests and their antibacterial potential is still a focus of research. For this purpose, in present research antibiotic ciprofloxacin (CPFX) has been selected as a parent compound and its analogues has been designed, synthesized and finally evaluated for their better antimicrobial activities. In current research, virtual screening has been performed to analyze the binding energies between the receptor and designed ligands. Those designed ligands showing better binding affinities than parent compound CPFX were short listed for synthesis. The present study also describes in silico prediction of drug-like properties of newly designed analogues by using different computational tools. The in silico screening of designed analogues indicated them qualified for the parameters of drug likeness also showing good bioactivity along with optimum pharmacokinetic properties. Overall results of in silico pharmacokinetic screening indicated that the newly designed compounds may be considered as a candidate for further drug development studies. In order to achieve this objective, six analogues of ciprofloxacin by introducing new functional groups at position C-3 and position C-7 have been synthesized. Structure of the analogues was confirmed by different techniques including IR, HNMR and mass spectroscopy. The antibacterial activity of the analogues was also assessed with the parent molecule against a series of Gram-positive and Gram-negative bacteria. Among all, the synthesized derivatives 3a, 3b and 7c showed diverse antimicrobial profile possessed a better activity in comparison to the ciprofloxacin. Docking studies of synthesized molecules revealed them as good antimicrobial candidates and their docking scores prove better binding as compared to the standard CPFX.