Abstract

IN SILICO EVALUATION OF SMALL MOLECULE INHIBITORS OF 1H 1,2,4-TRIAZOLES AND 2,4,5-TRISUBSTITUTED IMIDAZOLES AGAINST 2 ABL TYROSINE KINASE.

Annapoorna Vadivelu?, C.Uma Maheswara Reddy and V. Gopal

ABSTRACT

Recent observations of literature suggest that molecular manipulation and combination of two or more moieties into one molecule have been the method of research. A series of 17 1H,1,2,4-triazoles and 2,4,5-trisubstituted Imidazoles were designed and docking simulation was performed using Glide to position compounds into the 2 ABL tyrosine kinase structure active site to determine the probable binding model. The designed compounds were evaluated for their druglikeness, physiochemical properties and energy minimization studies were carried out for the designed compounds using chem biodraw and OSIRS. Further ADME properties such as bioavailability, distribution, metabolism and toxicity were studied using ACD/I Labs. The molecular docking of compounds revealed a hydrogen-bonding interaction, lowest energy value and effective docking score with the side chain of PHE109, suggesting this residue as a potential target site useful for enhancing 2 ABL tyrosine kinase inhibition. Based on the results of in silico studies compounds A7, A8, A13, AA18 and AA14 were found to have comparatively good oral bioavailability, nill genotoxicity and against 2 ABL tyrosine kinase.

Keywords: 2 ABL tyrosine kinase, 1H-1,2,4-triazole, 2,4,5-trisubstituted Imidazoles, Docking, Virtual screening, Physiochemical properties, Energy minimization studies and ADME.