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

Introduction: 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.

Objectives: The aim is to isolate and evaluate bioactive compounds from Laserpitium L. species with anticancer potential.

Material And Methods: 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 in vitro and in vivo, whereas molecular modeling, docking, and ADME predictions were conducted using Schrödinger software.

Results: 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.

Conclusion: Compounds 7 and 9, representing new nordaucane and sesquiterpene lactones, have not been previously reported. In vitro cytotoxicity revealed that compound 7 exhibits potent anti-cancer activity against MCF-7 cells, whereas compound 9 showed reduced cytotoxicity. In vivo 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.