In vitro and in silico analysis for elucidation of α-amylase and α-glucosidase: Synthesis, structural confirmation and drug likeness of benzothiazole derived thiazole base bis-Schiff base derivatives

Abstract

In this study, we have synthesized S-substituted benzothiazole derived thiazole bearing bis-Schiff base derivatives (1–19) and characterized via different spectroscopic techniques including NMR and HR-EIMS and then screened against α-amylase and α-glycosidase. All the analogues show excellent inhibitory capability. Analogues 1 (IC50 = 3.18 ± 0.72 µM and 2.30 ± 1.80 µM) and 4 (IC50 = 1.40 ± 0.59 µM and 2.10 ± 0.78 µM) were found to be the strongest among the all in contrast with standard drug acarbose (IC50 = 4.30 ± 0.18 and 6.45 ± 1.84 µM) for α-amylase and α-glycosidase. Some derivatives show good potency against both the enzymes while few were found moderately potent. For all the molecules structure–activity relationship was carried to determine the decrease/increase in potency due to steric hindrance, bulky nature, position, type, size, quantity of the substituent/s on phenyl rings. Molecular docking and ADME analysis were carried out to signify the binding interactions of the most potent derivatives with the active site of enzymes.

Keywords

• Diabetes Mellitus
• Benzothiazole
• Bis-Schiff base
• SAR
• Docking study and ADME