Abstract

DESIGN AND ANTIFUNGAL ACTIVITY OF NOVEL PYRIDYL TETRAZOLE DERIVATIVES AS CYP-51 INHIBITORS

Shiny George* and P. Shanmugapandiyan

Abstract

Molecular docking is an important tool of molecular modelling system which provides the ligand-protein interaction through four force fields by orientation and translation. Docking is the identification of the lowenergy binding modes of a small molecule or ligand, within the active site of a macromolecule or receptor whose structure is known. A new series of 2-(5-(substituted phenyl)-1H-tetrazol-1-yl) pyridine derivatives were designed as cytochrome P450 inhibitors based on docking studies and oral bioavailability scores based on Lipinski’s rule evaluation. To identify potential anti-fungal lead compounds among compounds 5a1-5j2, docking calculations were performed using Autodock v3.0 into the 3D structure of the catalytic site of CYP 51 enzyme (pdb code: 1EA1). Autodock score of the novel compounds showed good fit against CYP 51. The compounds which showed good fit were synthesized and were screened for antifungal activity against C. albicans and A. fumigatus. Minimum Inhibitory Concentration was determined by broth dilution method and were in the range of 12.5-50 μg/ml.

Keywords: pyridine, tetrazole, antifungal, docking.