Novel Nordaucane Sesquiterpenoid and Sesquiterpene Lactone From Laserpitium Species: Isolation, Structure Elucidation, InVitro, InVivo, and In Silico Evaluation as Anticancer Agents.

Abstract

This study explores the cytotoxic activity-guided isolation of the underground parts of Laserpitium hispidum M. Bieb and Laserpitium petrophilum Boiss. & Heldr., which have not been previously investigated. The aim is to isolate and evaluate bioactive compounds from Laserpitium L. species with anticancer potential. This study involves bioactivity-guided isolation and structural studies of the pure compounds utilizing NMR, UV-Vis, IR spectroscopies, and HRMS. The cytotoxic activity of the isolated compounds was evaluated invitro and invivo, whereas molecular modeling, docking, and ADME predictions were conducted using Schrödinger software. The study isolated phenylpropanoids (laserine (1), latifolone (2), myristicin (3)), sterol (stigmasterol (4)), polyenes (falcarindiol (5)), sesquiterpene lactone (11-hydroxybadkhyzin (6)), and nordaucane sesquiterpene (norlasidiol angelate (7)) from L. hispidum, whereas L. petrophilum yielded 10β-acetoxy-8α-angeloyloxy-6αH,7αH-guaian-3-en-12,6-olide (8), 10β-acetoxy-8α-senecioyloxy-6αH,7αH-guaian-3-en-6,12-olide (9) and acetylisomontanolide (10). Molecular docking simulations revealed stable interactions between compounds 7 and 9 with estrogen receptor α (ERα) and vascular endothelial growth factor receptor 2 (VEGFR2), with compound 7 showing superior stability and binding affinity. In silico ADME predictions indicated favorable pharmacokinetic properties, including high oral absorption. Compounds 7 and 9, representing new nordaucane and sesquiterpene lactones, have not been previously reported. Invitro cytotoxicity revealed that compound 7 exhibits potent anti-cancer activity against MCF-7 cells, whereas compound 9 showed reduced cytotoxicity. Invivo testing in Caenorhabditis elegans supported these findings, suggesting safety and efficacy in organisms. In silico results emphasize the potential of these compounds, with compound 7 promising due to its stability and strong binding affinity.