Synthesis, anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

E Praveenkumar; Nirmala Gurrapu; Prashanth Kumar Kolluri; Vishwanadham Yerragunta; Bharathi Reddy Kunduru; N J P Subhashini

doi:10.1016/j.bioorg.2019.103056

Synthesis, anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

Bioorg Chem. 2019 Sep:90:103056. doi: 10.1016/j.bioorg.2019.103056. Epub 2019 Jun 11.

Authors

E Praveenkumar¹, Nirmala Gurrapu¹, Prashanth Kumar Kolluri¹, Vishwanadham Yerragunta², Bharathi Reddy Kunduru³, N J P Subhashini⁴

Affiliations

¹ Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana 500 007, India.
² Bio-organic & Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and Research (VIPER), Narsapur, Medak, Telangana 502 313, India.
³ Department of Genetics and Biotechnology, University College of Science, Osmania University, Hyderabad, Telangana 500 007, India.
⁴ Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana 500 007, India. Electronic address: njsubhashini@osmania.ac.in.

PMID: 31276952
DOI: 10.1016/j.bioorg.2019.103056

Abstract

11-Beta-Hydroxysteroid dehydrogenase-1(11β-HSD1) inhibitors are one of the emerging classes of molecules to fight against diabetic complications. A novel series of 4-(1-substituted-1H-1,2,3-triazol-4-yl)-1,4-dihydropyridine derivatives were synthesized and evaluated for their anti-diabetic activity. Two compounds showed anti-diabetic activity very effectively. To clarify the mechanism of action of these compounds, the most potent compounds (5g and 5h) of the synthesized analogs were further studied by testing its 11-Beta Hydroxysteroid dehydrogenase-1 inhibitory activity through in vitro enzymatic experiments. The results showed that the 11β-HSD1 inhibitory activity of compounds 5g and 5h was stable and efficient. Molecular docking studies revealed compounds 5g (-9.758) and 5h (-8.495) to have a stable binding patterns to the human 11-Beta-Hydroxysteroid dehydrogenase-1.

Keywords: 1,2,3–Triazole; 11-BetaHydroxysteroid dehydrogenase-1(11β-HSD1) inhibitors 1, 4-dihydropyridine; Diabetic agents and molecular docking studies.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
Animals
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / enzymology
Diabetes Mellitus, Experimental / pathology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Mice
Models, Molecular
Molecular Docking Simulation
Structure-Activity Relationship

Substances

Enzyme Inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1