Four New Perforane-Type Sesquiterpenes from Laurencia obtusa (Hudson) J.V. Lamouroux as Potent Lung Cancer Inhibitors: Isolation, Structure Elucidation, Cytotoxicity, Molecular Docking, Dynamics, and ADME Studies

High Resolution Image Download MS PowerPoint Slide The red alga genus Laurencia (Rhodomelaceae) is a prolific source of halogenated secondary metabolites, particularly sesquiterpenes with diverse carbon skeletons and significant biological activities. In this study, four new perforane-type sesquiterpenes ( 1 – 4 ), including two halogenated and two nonhalogenated compounds, were isolated from Laurencia obtusa (Hudson) J. V. Lamouroux. Their chemical structures were elucidated using comprehensive spectroscopic techniques, including 1D- and 2D-NMR, and LC-HRMS. The cytotoxic potential of the isolated compounds was evaluated against human lung adenocarcinoma (A549) cells, revealing notable antiproliferative effects. To explore the molecular basis of their activity, molecular docking and molecular dynamics simulations were performed targeting key oncogenic receptors VEGFR1, VEGFR2, and EGFR. The results demonstrated strong binding affinities and stable interactions within the active sites of these targets. Furthermore, ADMET analyses predicted favorable pharmacokinetic profiles and acceptable toxicity parameters for the isolated compounds. These findings suggest that the newly identified perforane-type sesquiterpenes from L. obtusa hold promise as potential candidates for the development of novel anticancer agents targeting lung cancer.