IN SILICO STUDIES OF SOME NEWLY DESIGNED BENZIMIDAZOLETHIAZOLIDINONE BASED ANTAGONISTS OF HUMAN ESTROGEN RECEPTOR

Abstract

Breast cancer is globally associated with majority of the women. Indeed, high estrogen levels are the most common subtype of breast cancer. Three different classes of estrogen receptor antagonists are frequently used to treat such kinds of breast cancers. Each of these interacts directly with the initiation and activation of the estrogen signalling pathway. However, new medicines must be developed because resistance limits the therapeutic effectiveness. In silico studies for drug discovery have become popular in recent years due to their low cost and quick execution. To develop novel therapeutics for breast cancer, three different series of benzimidazole compounds targeting the estrogen receptor were docked. Among these three series, benzimidazole fused with pyrazole showed significant results and the leading compound was 32 based on docking results. The docking data was further validated by executing molecular dynamics (MD) simulations for the stability of designed leads within the macromolecular cavity in relation to time. Therefore, it is proposed that the pyrazole fused benzimidazole nucleus can be a promising pharmacophore for developing novel anticancer therapeutics for breast cancer.