Hybrid Pyrazole‐Tetrazole Derivatives with High α‐Amylase Inhibition Activity: Synthesis, Biological Evaluation and Docking Study

Abstract

The elaboration of some N‐alkylated pyrazole‐tetrazole derivatives is reported. The structures of the newly ones are verified using NMR and FTIR spectroscopies, mass spectrometry as well as elemental analysis. Their potencies to inhibit the α‐amylase enzyme were evaluated using spectrophotometric method and the obtained results showed that some of them were extremely potent with respect to the used positive control. The structure activity relationship showed that the α‐amylase inhibition activity depends on the alkylation position as well as the nature of the alkyl moiety and the alkylation at the N1 position with a donor group improves the α‐amylase inhibition activity. Docking study was also performed and the obtained results support the experimental results in the case of the alkylation position effect. These findings suggest that the molecules reported in this study may be used as good drug candidate to treat Type 2 diabetes.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents

“…Pyrazole- N -acetyl pyrazole-benzofuran derivative A demonstrated powerful antibacterial activity toward Escherichia coli and also a drug-likeness model score (DLS) equal to 0.83 ( Elsherif et al, 2020 ). Pyrazole-tetrazole derivative B (IC 50 = 3.45 × 10 −5 mg/ml) acts as an anti-diabetic agent, inhibiting the α-amylase enzyme more than acarbose (IC 50 = 0.26 mg/ml) nearly 10,000 times ( Harit et al, 2022 ). Coumarin-pyrazole derivative C displays high inhibitory activity as an anti-Alzheimer's agent toward acetylcholinesterase (AChE) (IC 50 = 4.41 ± 0.53 µg/ml), comparable to galanthamine (IC 50 = 6.27 ± 1.15 µg/ml) ( Benazzouz-Touami, et al, 2022 ) ( Fig.…”

Tetrazolopyrimidine-tethered phenothiazine molecular hybrids: synthesis, biological and molecular docking studies

“…10 Similarly, tetrazole derivatives incorporated with a diverse range of other structural motifs have exhibited various biological characteristics including CNS stimulant, analgesic, antibacterial, anticancer, antifungal, anticonvulsant, antiinflammatory, antidiabetic, antiproliferative, antitubercular, antimalarial, antidepressant, and anticardiovascular properties. [11][12][13][14][15][16][17][18][19][20][21] Tetrazole is a five-membered heteroaromatic motif that is acidic in nature (pK a is akin to carboxylic acid) and ionizes at physiological pH. 22 As is known, the tetrazole moiety possesses four nitrogens that can serve as both bifurcated (multicenter) and linear hydrogen bond donors as well as acceptors.…”