Synthesis, docking, and evaluation of novel thiazoles for potent antidiabetic activity

• Published in: Medicinal chemistry research Vol. 26; no. 6; pp. 1306 - 1315
• Main Authors: Sravanthi, T. V., Sajitha Lulu, S., Vino, S., Jayasri, M. A., Mohanapriya, A., Manju, S. L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2017; Springer Nature B.V
• Subjects: Acarbose; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Diabetes mellitus; Enzymes; Glucocorticoids; Hydrogen bonding; Hydrogen bonds; Indoles; Molecular docking; Molecular dynamics; Original Research; Pharmacology/Toxicology; Pyrazoles; Thiazoles; α-Amylase; α-Glucosidase; Heteroaryl substituted pyrazoles; Molecular dynamics simulation; Antidiabetic activity; Molecular docking
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-017-1851-8

In this study, a series of novel substituted pyrazoles containing indole and thiazole motifs were synthesized and evaluated for their antihyperglycemic activity against α -amylase and α -glucosidase enzymes. Among them, 2-(5-(1 H -indol-3-yl)-3-phenyl-1 H -pyrazol-1-yl)-4-(4-bromo phenyl) thiazole ( 3f ) was identified as the best antihyperglycemic activity (IC 50  = 236.1 µg/mL) in comparison with the standard drug (acarbose, IC 50  = 171.8 µg/mL). Through reverse screening, glucocorticoid receptor (1NHZ) was identified as the best target and molecular docking studies was performed to understand the interaction of the molecules to the active sites of 1NHZ. The docking study was then conducted against the enzymes ( α -amylase (4X9Y) and α -glucosidase (2QMJ)) used in the in vitro studies. A molecular dynamic simulation experiment was conducted to analyze the behavior of the docked complex. The analysis confirmed the stability of the docked complex in terms of energy and hydrogen bonds. In vitro and in silico evaluations thus generate an interesting insight toward exploring heteroaryl substituted pyrazoles as potent therapeutic antidiabetic agents.