In silico molecular docking against C-KIT Tyrosine Kinase and ADME studies of 3-Ethyl-2-(2,3,4-trifluoro-phenylimino)-thiazolidin-4-one derivatives

Abstract

Thiazolidin-4-one derivatives have been hailed as “wonder nucleus” due to their profound biological activities. A number of derivatives with variable functional groups attached to the five-membered heterocyclic ring which have been synthesized and further subjected to molecular docking studies, against C-KIT Tyrosine kinase target protein (1T46). The interactions, binding and affinity variations due to differences in functional groups have been studied using ChemDraw Ultra 7.0, RCSB – Protein Data Bank, BIOVIA Discovery Studio Visualizer 2021, MGL AutoDock Tools, AutoDock Vina and Vina Split software. The docking studies showed good interaction of the synthesized molecules with the 1T46 target protein. The ADME studies of these molecules have also been studied to identify which of the synthesized molecules have the potential to cross the Human Intestinal lining (HIA), as well as the BBB barrier. Out of the 18 molecules studied, 12 of them showed good potential to be absorbed by the intestine out of which only one molecule was able to show potential to cross the BBB barrier. There were 4 molecules that could not cross both the barrier. These studies could reveal which functionalities present attached to the thiazolidin-4-one could assist in human intestinal absorption and the crossing of the BBB barrier.