Isolation of Megastigmanes from Ficus sycomorus and In Silico Design of Novel Cyclohexenone Derivatives as Tubulin Inhibitors for Breast Cancer Therapy

Dauda Garba (University of Abuja Nigeria, Nigeria)

LinkedIn: Dauda Garba

Abstract: Breast cancer demands novel therapies with improved efficacy and reduced toxicity. Tubulin, particularly the colchicine-binding site, is an ideal target for disrupting microtubule dynamics. While medicinal plants offer chiral bioactive compounds, determining their absolute configuration is challenging. This study integrates phytochemistry and computational design to develop cyclohexenone-based tubulin inhibitors. Two megastigmane derivatives, vomifoliol (A1) and its 13-hydroxy analog (A2), were isolated from Ficus sycomorus and characterized via NMR, LCMS, and ECD. Guided by their scaffold and SAR, fourteen derivatives were designed in silico. SwissADME and ProTox-III confirmed drug-likeness and favorable ADMET profiles. Molecular docking against tubulin (PDB: 1SA0) identified six compounds with superior binding (−8.0 to −9.0 kcal/mol) over colchicine (−7.9 kcal/mol). Lig9 showed the strongest affinity (−9.0 kcal/mol), with key interactions at CYS241, LEU242, and ILE378. These results position Lig9 as a promising lead for breast cancer therapy, warranting experimental validation.