Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents.
Bioorg Chem
; 120: 105586, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35051706
ABSTRACT
This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti-diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazole-triazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP-4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents.
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Experimental
/
Inibidores da Dipeptidil Peptidase IV
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article