Ciprofloxacin analogues: drug likeness, biological and molecular docking studies

Abstract

The search for new antimicrobial agents due to the development of antimicrobial resistance is one of the greatest points of concern among medicinal chemists. It has been observed that the infections due to the antimicrobial resistance pathogens are one of the reasons for the mortality. Therefore, it is really important to find out some new low molecular weight antimicrobial drugs with different mode of action. Despite of being a better antibiotic, ciprofloxacin represented resistance against many pathogens. Herein, this study reported the synthesis of novel analogues of ciprofloxacin (1) including 1,3,4-oxadiazole, thiazolidine-4-one, 1,3,4-oxazoline, 1,2,4-triazole, Schiff's base, hydrazide, and 1,3,4-thiadiazole (2–8), following their computational assessment. All analogues were then synthesized and characterized using FT-IR, NMR, Mass spectroscopy, etc. The prepared analogs were then assessed for antimicrobial properties against bacterial pathogens and fungal isolates using disc diffusion and serial dilution methodology. To observe the toxicity of the prepared analogs the MTT assay was performed against HepG2 cells. The receptor glucosamine-6-phosphatase (GlcN-6P) and lanosterol 14-alpha-demethylase (CYP51) were used for the molecular docking assay using Auto Dock Tools-1.5.6 to evaluate the degree of hydrogen bonding and binding affinities. It was observed that analogue (2) established strong hydrogen bonds with the both receptors, with great binding affinities.