A Molecular Screening of HER2 Inhibitors from Curcuma zedoaria

Abstract

Breast cancer is the most commonly diagnosed cancer among women and leading the second most cause of cancer death worldwide in 2020. Human Epidermal Growth Factor Receptor 2 (HER2) is part of four members of the HER2 receptor family leading to proliferation, differentiation, and inhibition of apoptosis. Overexpression of HER2 is associated with a more aggressive disease with higher recurrence rates. The various bioactivity of the active substances from natural compounds has been tested as inhibitors, including white turmeric (Curcuma zedoaria). In several studies, extracts and essential oil of this plant showed promising antioxidant properties and cytotoxic against cancer cell lines. Therefore, this study predicts the potential of bioactive compounds of C. zedoaria targeting HER2 through molecular docking simulations. The conformational stability formed is the main parameter in the docking affinity assessment. The result showed that six out of 33 compounds from C. zedoria had potential as HER2 inhibitors. The binding affinity of dihydrocurcumin, curcumin, tetrahydrodemethoxycurcumin, zerumin A, demethoxycurcumin and bisdemethoxycurcumin were -7.4359 kcal/mol, -6.8372 kcal/mol, -6.6454 kcal/mol, -6.3360 kcal/mol, -6.3148 kcal/mol and -6.3148 kcal/mol, respectively. The inhibitory action of the compounds was also validated by comparing it with the reference compound lapatinib. Further research is needed to validate the above data.