European Journal of Molecular & Clinical Medicine

Abstract

Development of new drug candidates for the treatment of cancer is under keen investigation since last few decades. Overexpression of carbonic anhydrase enzyme leads to development of hypoxic cancer. Many drug candidates have been already reported against carbonic anhydrase, but they are associated with toxicity and drug resistance issues. Therefore, in order to develop new drug candidates as carbonic anhydrase inhibitors, we have designed a libarary of 96 compounds possessing two heterocyclic moieties (thiophene and triazole).The designed molecules were further subjected to molecular docking against carbonic anhydrase enzyme (PDB ID 1XPZ) using GOLD and MOE software. The Gold and MOE scores of all the compounds were calculated among which 6 best compounds were screened and their binding patterns with the receptor were observed. Further, ADME, drug likeliness and toxicity characteristics have been predicted by using Swiss ADME predictor and preAdme tool, Lazar and protox. All the parameters were in the specified limits and followed the Lipnski’s rule. However, compound 67 has showed best interactions when compared with internal ligand by forming hydrogen bond interactions with THR 200, HIS 94, THR 199 and metal interaction with Zn 262. Validation of docking procedure was done and RMSD value was found to be 1.76Å. Interactions of best 6 compounds were predicted on MOE software which showed similarity in the binding pattern as predicted by GOLD software