In vitro and in silico analysis of anticancer activity of terpenoids of Dittrichia viscosa (L.) Greuter essential oil

Abstract

There is a continuous global search for new anticancer agents from natural sources. In this study, the essential oils of Dittrichia viscosa (L.) Greuter leaves (DVEO) were extracted by hydrodistillation and chemically profiled using GC-MS, identifying 25 compounds, mainly terpenoids. DVEO in vitro cytotoxicity assays against six human cancer cell lines (MDA-MB-231, A549, MCF7, SKOV3, HepG2, and HCT116) revealed strong antiproliferative effects (IC50 between 16.2 and 30 μg/mL), with selective safety against normal neonatal human fibroblasts (HDFn, IC50 42 μg/mL) [1]. Virtual screening and network pharmacology analysis including ADMET screening, protein-protein interaction analysis, and molecular docking of the predominant compounds -11-hydroxy-eremophyl-6(7),9(10)-dien- 8-one (30.56% area), 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol (10.87%), and geraniol (17.93%) - identified MMP9, PTEN, and STAT3 as key targets [2,3]. The lead compound, 11-hydroxy-eremophyl- 6(7),9(10)-dien-8-one, showed a high binding affinity with MMP9 (−7.3 kcal/mol), PTEN (−7.0 kcal/mol), and STAT3 (−6.8 kcal/mol). The strong binding affinity of these compounds with the targets was confirmed through molecular dynamics simulation and binding free energy calculations (−36.61 kcal/mol), demonstrating stable binding, structural compactness, and residual fluctuations upon compound binding [3,4]. Density Functional Theory (DFT) further confirmed the compound’s electronic stability and reactivity [5]. These findings establish D. viscosa essential oil, particularly its prevalent terpenoids, as promising candidates for anticancer drug development.