Computational Analysis to Evaluate the Anticancer Potential of Natural Usnic Acid Derivatives for the Management of EGFR-Kinase-Associated Breast Cancer

Abstract

Breast cancer is the most common disease in the world, with about 2 million new cases reported in 2018. It also accounts for 6.6% of all cancer-related deaths worldwide and 11.6% of all diagnosed cases. The goal of this work is to identify potential therapeutics against the EGFR protein from the naturally occurring UA derivatives that may be used through several in-silico techniques to treat breast cancer. These chemicals showed activity against breast cancer using the PASS predictions, with a score of Pa > 0.7 and Pi < 0.005. The reference drug, gefitinib, has a binding energy of –7.9 kcal/mol, whereas these compounds displayed binding energies of –8.0 to –8.3 kcal/mol into the EGFR protein’s active site. To evaluate the stability and binding posture of lead complex during the docking experiment, 200 ns of molecular dynamic simulation analysis were performed and showed that Usimine B-EGFR complex showed more stability than the reference complex. Furthermore, the pharmacokinetics and DFT studies showed that Usimine B compound is safe, effective and strong drug qualities. Overall, Usimine B has shown strong binding affinity towards the EGFR protein of breast cancer, good pharmacokinetics and DFT properties. Further medication research and optimization against breast cancer treatment may result from the identification of Usimine B as a breast cancer agent that targets the EGFR protein.