Multicomponent reaction for the synthesis of new 1,3,4-thiadiazole-thiazolidine-4-one molecular hybrids as promising antidiabetic agents through α-glucosidase and α-amylase inhibition.

[Display omitted] • A new series of 1,3,4-thiadiazole-thiazolidine-4-one molecular hybrids were developed. • A three-component reaction was established in the presence of p -toluene sulfonyl chloride and triethylamine. • The synthesized hybrids were screened for their antidiabetic, antioxidant and antimicrobial activities. • Compound 4e bearing a para -thiomethyl unit showed the most potent inhibition of α -glucosidase and α -amylase. A simple and efficient protocol was developed to synthesize a new library of thiazolidine-4-one molecular hybrids (4a-n) via a one-pot multicomponent reaction involving 5-substituted phenyl-1,3,4-thiadiazol-2-amines, substituted benzaldehydes and 2-mercaptoacetic acid. The synthesized compounds were evaluated in vitro for their antidiabetic activities through α -glucosidase and α -amylase inhibition as well as their antioxidant and antimicrobial potentials. Compound 4e exhibited the most promising α -glucosidase and α -amylase inhibition with an IC 50 value of 2.59 μM, which is ~1.5- and 14-fold superior as compared to the standard inhibitor acarbose. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the phenyl rings had a significant effect on the inhibitory potency. [ABSTRACT FROM AUTHOR]