Molecular docking studies of N-Heterocyclic Carbene molecules with Thioredoxin Reductase and DNA

Abstract

Thioredoxin which is induced by thioredoxin reductase causes the proliferation of cancerous cells and metastasis due to its effects on cell growth, besides its regulatory effects on the amount of reactive oxygen species. One of the procedures recently used in cancer treatment is thioredoxin reductase inhibition. Different types of bioactivities of NHC and metal-NHC complexes have been studied and anti-cancer is one of these activities. In addition to in-vitro anticancer activity, molecular docking methods are also one of the important methods used in drug design. This method achieves foresight about future studies and the mechanisms that are difficult to analyze experimentally. In this study, previously synthesized and characterized [1-(2-methyl-2-propenyl)-3-(4-methylbenzyl) benzimidazolium]+ (1a) and [1-(2-methyl-2-propenyl)-3-(4-isopropylbenzyl) benzimidazolium]+ (1b) molecules and their Ag(I)-NHC complexes (2a and 2b) were investigated using molecular docking method for thioredoxin reductase. In addition, the interaction of these molecules with DNA was evaluated. 2b has the best binding energy of -8.95 kcal/mol with the region that comprised Ile10, Phe254, Ala38, Val41 of thioredoxin reductase. Also, ligands interacted with Cyt11, Gua10, Cyt9, and Thy8 while complexes interacted with Ade5, Ade6, Thy7, and Thy8 part of DNA.