Design, In Silico Study, Isolation Of Pinostrobin From Fingerroot (Boesenbergia pandurata), Synthesis Of 5-O-Benzoylpinostrobin Derivatives, and Cytotoxic Activity Test As Potential Antibreast Cancer Agents

Breast cancer poses a persistent global health burden, driving the search for innovative treatments. Natural products, such as flavonoids like pinostrobin from fingerroot (Boesenbergia pandurata), are recognized for their potential bioactivity. Chemical modification of these compounds is a well-established strategy to enhance therapeutic efficacy. The objectives of this research were to enhance the cytotoxic activity of pinostrobin against T47D breast cancer cells through chemical modification, predict in silico ADMET and molecular docking profiles, synthesize novel derivatives, and determine their in vitro cytotoxicity. This study employed a multi-faceted approach, including computational design and optimization of 5-O- benzoylpinostrobin derivatives (molecular docking, ADMET, QSPR), pinostrobin extraction from fingerroot, microwave-assisted synthesis of 5-O-benzoylpinostrobin, and in vitro cytotoxicity assessment against T47D and Vero cells (MTT assay). In silico studies identified 5-O-(4-t- butylbenzoyl)pinostrobin as a promising ligand for ERα, PR, EGFR, and HER2 receptors, supported by favorable ADMET profiles. Synthesis of 5-O-benzoylpinostrobin and 5-O-(4-t- butylbenzoyl)pinostrobin was achieved. 5-O-benzoylpinostrobin demonstrated the highest cytotoxic activity against T47D cells (IC50 85.47 µg/mL, SI 4.52), albeit lower than doxorubicin. Consequently, the data presented support 5-O-benzoylpinostrobin as a potential therapeutic agent for breast cancer, and we recommend further studies to include optimization of synthetic pathways, in vivo investigations, and drug delivery development.

Keywords: Pinostrobin, fingerroot, molecular docking, in vitro cytotoxicity, 5-O-benzoylpinostrobin