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 α-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 α-amylase. The anti-diabetic studies revealed that compound DM_3A (IC₅₀ = 19.26 ± 0.23) followed by 3-(3-(diethyl carbamoyl) thioureido) benzoic acid (IC₅₀ = 21.89 ± 0.06) were more potent against α-amylase and α-glucosidase, comparable to that of standard drug acarbose. DM_3A displayed best antioxidant potential (DPPH IC₅₀ = 7.97 ± 0.23 µg/ml, TAC IC₅₀ = 8.19 ± 0.64 µg/ml, Total reducig power IC₅₀ = 8.19 ± 0.23 µg/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 DM_3A might be possible lead compound. Further, in-vivo research is recommended to fully determine the biological spectrum of these newly synthesized thiourea derivatives.