Acetyl-CoA synthetase and isopentyl-diphosphate isomerase inhibition underscore columbin anti trypanosomiasis: Computational studies.

Abstract

Columbin, a plant-derived compound may represent a key frontier in the treatment of blood-stage trypanosomiasis. To be a viable future drug candidate, there is an urgent need to decipher its physiological target along the mevalonate pathway and to modify the original scaffold in order to improve its physicochemical properties and its ability to cross the blood-brain barrier. In this study, homology modeling method was used to generate the 3D models of the putative targets along the mevalonate pathway. Autodock-vina was used to dock columbin into the ligand pockets of the targets. The result showed that acetyl-CoA synthetase (-9.3 kcal/mol Vs -9.3 kcal/mol standard) and isopentyl- diphosphate isomerase (-9.6 kcal/mol vs. -8.5 kcal/mol standard) were the most plausible targets of columbin. In conclusion, acetyl-CoA synthetase and isopentyl-diphosphate isomerase inhibition may underscore the anti-trypanosomal actions of columbin targeting isoprenoid metabolism.