Novel Pyrazolo[3,4‐d]pyrimidine‐Containing Amide Derivatives: Synthesis, Molecular Docking, In Vitro and In Vivo Antidiabetic Activity

Abstract

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.[a] Dr.

Zinc Oxide Nanoparticles and Synthesized Pyrazolopyrimidine Alleviate Diabetic Effects in Rats Induced by Type II Diabetes

“…In addition, ZnO NPs have been discovered to be a powerful metal that enhances glucose consumption and metabolism via its potent effect on hepatic glycogenesis via insulin signaling pathway actions . Moreover, pyrazole [3,4-d] pyrimidine-containing amide derivatives could be developed as oral hypoglycemic medications with a little more lead optimization …”

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“…Trifluoro ethyl hydrazine and malononitrile were reacted in methanol at reflux condition for 3 h to obtain intermediate that was used for final product with good yield after a series of steps such as amide formation, cyclization, chlorinated, nucleophilic substitution, reduction, and coupling. 219 The synthesis of tetrahydropyrmidine was done viz Bignelli condensation followed by microwave irradiation. To a mixture of benzaldehyde, urea, and ethyl acetoacetate in a round bottom flask, concentrated hydrochloride acid was added and poured into a china dish for microwave 180 watts irradiation for one minute.…”

“…However, compound 8k had also a score 48.12, which showed hydrophobic contacts with Thr163, Tyr62, Trp59, Ile51, Leu165, along H-bonding with Glu233, Arg195 and Asp197. 219 …”

Design, Synthesis, and the Effects of (E)-9-Oxooctadec-10-en-12-ynoic Acid Analogues to Promote Glucose Uptake

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