Biological and computational evaluation of carbazole-based bis-thiosemicarbazones: A selective enzyme inhibition study between α-amylase and α-glucosidase

Abstract

Background and Aims: Carbazole heterocyclic systems are an important class of chemicals that have been reported as valuable antidiabetic agents in the literature. Uncoincidentally, the ayurvedic antidiabetic plant Murraya koenigii Spreng (Curry tree) was the source of the first carbazole alkaloids. Another important class of chemicals in terms of antidiabetic activity is thiosemicarbazones. The hybridization of these fragments can create new potential inhibitors for α-amylase and α-glucosidase enzyme inhibitions, which is one approach controlling post-prandial hyperglycemia in type 2 diabetes patients. Methods: The four carbazole-based thiosemicarbazone compounds (4a-d) have been selected from the group library and α-amylase and α-glucosidase inhibition potencies have been evaluated. A molecular modelling study has also been carried out to provide a complementary study on how the molecules behave in terms of the enzymes’ catalytic properties. Results: All compounds showed higher potencies than the standard acarbose in terms of α-glucosidase inhibition and very low inhibitions toward α-amylase compared to acarbose. Having the number of hydrophobic interactions determine the po- tency of the compounds was crucial with compound 4a being shown to provide the highest number of conventional H bonds and the highest percentage of inhibition values for both enzymes. Conclusion: Carbazole-based thiosemicarbazone compounds have been found to be promising candidates in terms of both their potency and relative selectivity for developing new inhibitors that lack the usual side effects of current drugs.

Keywords

• α-Amylase
• α-Glucosidase
• Carbazole
• Molecular Docking
• Thiosemicarbazones

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