Synthesis and α-glucosidase inhibition studies of norfloxacin-acetanilide hybrids

• Published in: Pakistan journal of pharmaceutical sciences 2021-09, Vol.34 (5(Supplementary)), p.1909-1915
• Main Authors: Walayat, Kamran, Ahmad, Matloob, Ali Ashfaq, Usman, Ali Khan, Zulfiqar, Sultan, Sadia
• Format: Article
• Language: English
• Subjects: Acarbose - chemistry; Acarbose - pharmacology; Acetanilides - pharmacology; alpha-Glucosidases; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Molecular Docking Simulation; Molecular Structure; Norfloxacin - pharmacology; Structure-Activity Relationship
• ISSN: 1011-601X
• DOI: 10.36721/PJPS.2021.34.5.SUP.1909-1915.1

α-Glucosidase inhibitors occupy a prominent position among the various treatments of type-2 diabetes mellitus (DM2). In this study, a series of new norfloxacin-acetanilide hybrid molecules were synthesized and screened for α-glucosidase inhibition activity. The synthetic methodology involves the synthesis of a series of α-bromoacetanilides by condensing bromoacetyl bromide with various substituted anilines. These α-bromoacetanilides were coupled with norfloxacin in DMF to get the titled hybrids. The structure elucidation of synthesized compounds were characterized by H NMR, C NMR and LC-MS. Finally, the compounds were screened for their α-glucosidase inhibition activity using acarbose as a reference drug (IC =58 μM). Among the tested compounds, 3i and 3j displayed potent α-glucosidase inhibition activity with IC values of 7.81±0.038 and 5.55±0.012 μM respectively. In-addition, 3m, 3f and 3k were demonstrated moderate alpha-glucosidase inhibition activities with IC values of 52.905±0.041, 23.79± 0.087 and 23.06±0.026 μM respectively. The structure-activity relationship was established with the help of molecular docking by using Molecular Operating Environment software (MOE 2014).