Anti-diabetic potential, crystal structure, molecular docking, DFT, and optical-electrochemical studies of new dimethyl and diethyl carbamoyl-N, N′-disubstituted based thioureas

Four new thiourea derivatives containing dimethyl and diethyl carbamoyl scaffolds have been synthesized by multicomponent methodology. Docking analysis of alpha-amylase with thioureas showed that the 3-(3-dimethyl carbamoyl) thioureido) benzoic acid can effectively bind to the hydrophobic cavity and form hydrogen bonding effectively with the HIS A:103, ASP A:326, ARG A:407, ARG A:411 of human pancreatic alpha-amylase. The anti-diabetic studies revealed that compound DM3A (IC50 = 19.26 +/- 0.23) followed by 3-(3-(diethyl carbamoyl) thioureido) benzoic acid (IC50 = 21.89 +/- 0.06) were more potent against alpha-amylase and alpha-glucosidase, comparable to that of standard drug acarbose. DM3A displayed best antioxidant potential (DPPH IC50 = 7.97 +/- 0.23 mu g/ml, TAC IC50 = 8.19 +/- 0.64 mu g/ml, Total reducig power IC50 = 8.19 +/- 0.23 mu g/ml) but insignificant hemolytic activity. Further, DFT, molecular electrostatic potential and optical-electrochemical studies were also performed to support the in-silico and in-vitro biological screening results. Finally, the pharmacological profile revealed that DM3A might be possible lead compound. Further, in-vivo research is recommended to fully determine the biological spectrum of these newly synthesized thiourea derivatives. (c) 2021ElsevierB.V. Allrightsreserved.

Automated summary

Four new thiourea derivatives were synthesized using multicomponent methodology. Among them, compound DM3A showed significant inhibitory activity against alpha-amylase and alpha-glucosidase. It also exhibited excellent antioxidant potential and negligible hemolytic activity.