Synthesis and characterization of some novel benzoyl thioureas as potent α-glucosidase inhibitors: In vitro and in silico

Abstract

A series of sixteen benzoyl thiourea derivatives was prepared in good to excellent yield (49–92 %). Eight out of sixteen were reported compounds. The structures of prepared derivatives were elucidated by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic (1H NMR) and carbon nuclear magnetic resonance (13C NMR), and mass spectroscopy (ESI-MS). The structure of two compounds TU-8 and TU-15 was further established by single crystal X-ray diffraction (SCXRD) studies. All of the prepared compounds were screened for their potential as α-glucosidase inhibitor and found to be more potent than standard acarbose. TU-8 and TU-14 were lead compounds with IC50 values 1.59 ± 0.04 µM and 0.60 ± 0.02 µM, respectively. All the prepared compounds were found to non-toxic to fibroblast 3T3-L1 cell lines. The structure activity relation was confirmed by various substituents on phenyl ring. Furthermore, the interaction of compounds with enzyme was confirmed by docking studies. This study proves that synthesized 1, 3-disubstituted thiourea derivatives are excellent α-glucosidase inhibitor and can be exploited to design novel therapeutics to cure type-II diabetes.