MOLECULAR DESIGN AND ANTI-BREAST CANCER ACTIVITY OF TUPICHINOL E IN HER2+ BREAST CANCER AND EGFR SENSITIZED TO OSMERTINIB THERAPYAbstract
The epidermal growth factor receptor is a tyrosine kinase receptor and its overexpression triggers cancers. EGFR inhibition is one of the most unique and popular technique for cancer treatment. There are various approved EGFR inhibitors like osmertinib, lapatinib, afatinib, etc. Huge natural products are discovered every year and Rhamnocitrin derivative Tupichinol E obtained from the Northern Sikkim plant Tupistra nutans is structurally similar to EGFR inhibitors. Structurally similar EGFR inhibitors, their modes of binding and mechanism of actions are a new way to select lead compounds for better alternatives. Therefore molecular docking is done to find a potential anti-EGFR flavonoid. Osmertinib shows binding energy -107.23 kcal/mol with EGFR, while Tupichinol E shows binding energy -98.89 kcal/mol. Tupichinol E shows 1.5 times more binding affinity than osmertinib. The compound binds to the EGFR at the same exact position as osmertinib and has the same docking poses. Tupichinol E binding to EGFR stabilises the protein structure and is a pharmacologically active substance that can be used against cancer due to its potent activity.
Adyasa Samantaray, Debasish Pradhan *, Lalatendu Mohanty and Nalini Ranjan Nayak
University Department of Pharmaceutical Sciences, Utkal University, Bhubaneswar, Odisha, India.
07 March 2023
05 May 2023
05 October 2023
01 November 2023