Exploring Benzoxazole Scaffolds: In-Silico Docking, ADME studies, and Synthesis for Breast Cancer Treatment

Abstract

Breast cancer is one of the most common cancers in women with more than 2 million cases in 2022, worldwide. Not a single reliable drug therapy has been developed for triple-negative breast cancer and resistance is developed against the established therapy. So, there is need to develop novel therapy for the same. The history deacetylase inhibitors (HDACi) show promises as selective anticancer therapies, as they induce chromatin remodelling and normalize altered gene expression. This project, thus, aims to increase the efficacy of Vorinostat on breast cancer by designing, synthesizing, and evaluating new benzoxazole-based derivatives of the drug. Several molecules were designed by changing the linker with different aromatic cap groups and benzoxazole rings. These were then further subjected to molecular docking and in-silico ADME analyses. These compounds possessed a strong affinity for HDAC6, especially compound 9c, which demonstrated significant antiproliferative activity against MCF-7 breast cancer cell lines with an IC₅₀ value of 24.1 μg/ml. The adherence of the compounds to Lipinski's rule showed advantageous pharmacokinetic characteristics, such as high gastrointestinal absorption and good bioavailability. The promising results suggest that these novel benzoxazole-based HDAC inhibitors could be a viable option for targeted treatment of breast cancer. More experimental and clinical research is required to determine their potential as effective therapeutic drugs, primarily in aggressive types of breast cancer such as triple-negative breast cancer.