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

Lalitha Gummidi; Nagaraju Kerru; Oluwakemi Ebenezer; Paul Awolade; Olakunle Sanni; Md Shahidul Islam; Parvesh Singh

doi:10.1016/j.bioorg.2021.105210

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

Bioorg Chem. 2021 Oct:115:105210. doi: 10.1016/j.bioorg.2021.105210. Epub 2021 Jul 26.

Authors

Lalitha Gummidi¹, Nagaraju Kerru¹, Oluwakemi Ebenezer¹, Paul Awolade¹, Olakunle Sanni², Md Shahidul Islam², Parvesh Singh³

Affiliations

¹ School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa.
² Department of Biochemistry, School of Life Sciences, University of Kwazulu-Natal, Westville Campus, Durban 4000, South Africa.
³ School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa. Electronic address: singhp4@ukzn.ac.za.

PMID: 34332231
DOI: 10.1016/j.bioorg.2021.105210

Abstract

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 IC₅₀ 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.

Keywords: 1,3,4-Thiadiazole; Antidiabetic activity; Thiazolidin-4-ones; α-Amylase inhibition; α-Glucosidase inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacology*
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Thiadiazoles / chemical synthesis
Thiadiazoles / chemistry
Thiadiazoles / pharmacology*
Thiazolidines / chemical synthesis
Thiazolidines / chemistry
Thiazolidines / pharmacology*
alpha-Amylases / antagonists & inhibitors*
alpha-Amylases / metabolism
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Thiadiazoles
Thiazolidines
1,3,4-thiadiazole
alpha-Amylases
alpha-Glucosidases