New pyrazole-tetrazole hybrid compounds as potent α-amylase and non-enzymatic glycation inhibitors

Abstract

The synthesis of eight novel pyrazole-tetrazole compounds are presented. Their structures are identified by NMR and FTIR spectroscopy, mass spectrometry as well as elemental analysis. Their in-vitro α-amylase inhibition and haemoglobin antiglycation activity were examined by spectrophotometric methods. All compounds possess both activities, especially molecules entitled 2-(1-((5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 4 and 2-(1-((1-ethyl-5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 8 which were found to be extremely potent compared to the positive controls. The SAR study proved the influence of the alkylation position of pyrazole derivative on the tetrazole ring, the nature of substituent on the tetrazolic carbon atom and the nature of the group at the nitrogen atom of the pyrazole ring on both α-amylase and glycation inhibition activity. Compounds 4 and 8 could be a good drug candidate to treat Type 2 diabetes.

Keywords: Antiglycation; DFT calculation; Docking; Pyrazole; Tetrazole; α-Amylase.