Design and Synthesis of Fluoroquinolone Derivatives as Potent α‐Glucosidase Inhibitors: In Vitro Inhibitory Screening with In Silico Docking Studies

Abstract

AbstractFluoroquinolones are extensively used in clinical applications as a crucial class of antibacterial medicine and have shown high potential for the treatment of several other diseases. This study is based on synthesis, structure elucidation and biological evaluation of various fluoroquinolone (enoxacin) analogues with electrophilic substitution of aromatic amine moiety of central enoxacin nucleus by benzyl halides. The synthesized derivatives were characterized on the basis of different chemical and physical measurements and structures were elucidated by various spectroscopic techniques (NMR, EI‐MS), including elemental (CHN), and X‐ray diffraction analysis. Furthermore these compounds were investigated for their potential α‐glucosidase inhibition activities and all synthesized analogues of fluoroquinolones were found to exhibit promising inhibition potential of 45.8±0.2 to 74.5±0.2 μM in comparison to IC50 value of 425.6±1.3 μM for standard inhibitor of α‐glucosidase1‐deoxynojirimycin. Further, docking of synthetic compounds were carried out by using α‐glucosidase I enzyme of Saccharomyces cerevisiaeas a target. The study provided an insight of the molecular interactions of fluoroquinolone derivatives with the enzyme that are in good agreement with the inhibitory activity of synthesized compounds and can be considered as a valuable tool for designing new drugs.