Pinostrobin and its derivatives as novel anti-breast cancer agents against human oestrogen receptor alpha: In silico studies of ADMET, docking, and molecular dynamics

Abstract

Background: Breast cancer is the main cause of cancer death among women. The issue is more complex due to the side effects and resistance of the currently used breast cancer drugs. Pinostrobin, a compound found in Boesenbergia pandurata, has anticancer activity. Modifying the structure of pinostrobin can improve drug bioavailability, reduce toxicity, and work more selectively. Objective: This study aimed to predict the potentials of pinostrobin and its derivatives as anti-breast cancer agents against human oestrogen receptors by an in silico approach. Methods: The pkCSM was utilised to predict the ADMET characteristics. The interaction of ligands with the binding site of the human oestrogen receptor alpha with PDB ID 3ERT was used for molecular docking using MOE, and AMBER was then used for molecular dynamic simulation. Results: Pinostrobin pentanoate had good pharmacokinetic properties and was neither mutagenic nor hepatotoxic. Based on molecular docking, it was more potent compared to pinostrobin, with binding free energy values of -7.849 kcal/mol. Furthermore, in the interaction stability evaluation using 100 ns molecular dynamic simulation by the MM-GBSA calculation method, pinostrobin pentanoate had a stable interaction with a total bond energy value of -9.943 kcal/mol. Conclusion: Pinostrobin pentanoate has the potential as an anti-breast cancer alternative through the human oestrogen receptor alpha.