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Novel Pyrazolo[3,4‐ d ]pyrimidine‐Containing Amide Derivatives: Synthesis, Molecular Docking, In Vitro and In Vivo Antidiabetic Activity
Author(s) -
Reddy Bijivemula N.,
Ruddarraju Radhakrishnam Raju.,
Kiran Gangarapu.,
Pathak Madhvesh,
Reddy Anreddy Rama Narsimha
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201900208
Subject(s) - acarbose , pyrimidine , in vivo , chemistry , amide , docking (animal) , stereochemistry , in vitro , amylase , enzyme , pharmacology , biochemistry , medicine , biology , microbiology and biotechnology , nursing
A new series of Pyrazolo[3,4‐ d ]pyrimidine containing amide derivatives ( 8 a‐l ) were designed, synthesized, and evaluated for their in vitro α‐amylase inhibitory activity. The IC 50 values of the target compounds ranged from 1.60±0.48 to 2.04±1.20 μM as compared to the standard acarbose 1.73±0.05 μM. All the Pyrazolo[3,4‐ d ]pyrimidine amide derivatives displayed good inhibitory activities, while seven analogs ( 8 d , 8 f , 8 g , 8 h , 8 i , 8 j and 8 k) exhibited more or less equipotent activity with IC 50 values 1.77±2.84, 1.65±0.45, 1.66±2.24, 1.73±0.37, 1.60±0.48, 1.75±0.36 and 1.64±0.03 μM respectively. Further, the most potent α‐amylase inhibitors 8 d and 8 k were also screened for their in vivo antidiabetic activity against alloxan induced diabetic rat model at the dose of 25 and 50 mg/kg. Oral administration of these tested compounds significantly reduced the fasting blood glucose levels in dose dependent manner. The hypoglycemic effects of these compounds were more evident at 3 h and 5 h after administration of tested compounds which was similar to the effect displayed by the positive control. In addition, the binding energies calculated from the docking studies with the α‐amylase enzyme (PDB ID: 1HNY) and biological activities indicate that the compounds containing nitro moiety on the phenyl group contributed significantly towards the antidiabetic activity.