Anti-proliferative Activity of Labdane Diterpenes Isolated from Polyalthia cerasoides and their Molecular Interaction Studies

Background: Polyalthia cerasoides is well known for its therapeutic effects and is extensively used by the tribal people of South India and Africa to treat infertility, toothache, inflammation, rheumatism, fever, and to combat stress. Objective: In the present research, the anti-proliferative potential of two bioactive compounds isolated from the stem bark of P. cerasoides (Roxb.) Bedd. of the Annonaceae family was investigated. Methods: The dried stem bark was powdered and subjected to extraction using methanol and further partitioned using petroleum ether. Yellow viscous oil was isolated from the petroleum ether fraction using column and preparative thin-layer chromatography. The chromatographic fractions were characterized using GC-MS. The anti-proliferative effect of the isolated compounds was assessed against HepG2 Cells using MTT- Cytotoxicity test. Furthermore, comparative in-silico docking studies were performed to predict the binding pattern of isolated molecules individually, as well as simultaneously with α, β-tubulin, a critical protein involved in the molecular mechanism of microtubule formation. Results: GC-MS analysis of yellow viscous oil from petroleum fraction confirmed the presence of two labdane diterpenes that were identified as 12E-3,4-Seco-labda-4(18),8(17),12,14-tetraen-3-oic acid, and methyl harvadate C by mass fragmentation analysis. The MTT-cytotoxicity assay showed the dose-dependent cytotoxic effect on HepG2 Cells. The comparative docking studies of the isolated compounds exhibited strong interactions with the α, β-tubulin protein. Conclusion: The prominent anti-proliferative effect exhibited by the isolated compounds, along with effective binding to α, β-tubulin protein, encourages their future utilization as prominent anti-cancer molecules.