In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts

<strong>Background and Aims:</strong> The roots of Asphodeline lutea are traditionally consumed in the diet of people from Mediterranean countries. The methanol root extracts of A. lutea have been proven to possess cytotoxic activity against the MCF-7 and MCF-10A cell lines. The goal of our investigation was to determine the physicochemical and pharmacokinetic properties, possible inhibition against CYP450 isoenzymes, and probable cytotoxic effect of some bioactive components isolated from A. lutea roots using in silico methods. <strong>Methods: </strong>The Absorption, distribution, metabolism, and excretion (ADME) profiles were determined using the freely available SwissADME server. To increase the robustness of the SwissADME results, further calculations with the QikProp module in Maestro were carried out. The docking studies were carried out with Glide. The Induced-fit docking (IFD) and Molecular Mechanics-Generalized Born Surface Area (MM/ GBSA) modules in Maestro were applied for recalculations. The anticancer activities were predicted by the online server CLC-Pred. <strong>Results:</strong> The in silico ADME studies identified chrysophanol and helminthosporin as suitable for future evaluations considering their optimal pharmacokinetic profiles. The former compounds adhere to all of Lipinski’s rule of five for drug likeness. The docking studies identified helminthosporin as a potential inhibitor of CYP1A2 and a weak CYP3A4 inhibitor. Chrysophanol, helminthosporin, asphodelin and 10, 7'-bichrysophanol are expected to manifest a strong cytotoxic effect against A2780cisR cell line. They exerted a strong to modest cytotoxic effect against HOP-18, RCC4 and M19-MEL cell lines. 1,5,8-trihydroxy-3- methylanthraquinone exhibited modest action against GIST430 cell line, while 10, 7'-bichrysophanol had moderate activity against A2780 and SW1990 cell lines. <strong>Conclusion:</strong> Our findings justify the future in vitro and in vivo studies of A. lutea plant extracts as potential anticancer agents.&nbsp;