Proton NMR

Gene

Computational chemistry

Nursing

Carbon-13 NMR

Organic chemistry

Enzyme

Chemistry

In vitro

Combinatorial chemistry

In silico

Acarbose

IC50

Triazole

1,2,4-Triazole

Pyrazoline

1,2,3-Triazole

Active site

Docking (animal)

Biochemistry

Pharmacophore

Molecular dynamics

Stereochemistry

Medicine

Journal of Molecular Structure

A series of molecular hybrids based on pyrazoline and 1,2,3-triazole pharmacophores were designed and synthesized as antidiabetic agents. The structures of all the derivatives were confirmed using 1H NMR, 13C NMR and HRMS. Moreover, the structure of one of the intermediate precursor was confirmed using single crystal X-ray diffraction. The anti-diabetic potential of all the synthesized compounds was explored in terms of α-glucosidase inhibition studies. All the compounds exhibited remarkable inhibition of α-glucosidase. The inhibition of enzyme by compound TPZ2 (IC50 = 41.29 ± 0.123) and TPZ8 (IC50 = 47.94 ± 0.246) was found to be more promising as compared to the reference drug i.e., Acarbose (IC50 = 60.68 ± 0.123). The inhibition of α-glucosidase was further supported by in silico docking studies. In order to explore the most favorable binding interactions the binding pose of lowest energy was then subjected to molecular dynamics studies. Both the ligands have reasonable interactions with the protein active site with average interaction energy of −270.88 kcal/mol and −273.90 kcal/mol for TPZ8 and TPZ2, respectively.

Synthesis, characterization, α-glucosidase inhibition and molecular modeling studies of some pyrazoline-1H-1,2,3-triazole hybrids