Antiproliferative activity of sesquiterpene lactones from Dittrichia viscosa (L.) Greuter: In vitro and in silico studies

Abstract

Plant-derived metabolites have provided promising leads in the search for safer anticancer chemo-therapies. Among these, sesquiterpene lactones, predominantly present in the genus of the Aster-aceae family, exhibit great structural diversity and a broad range of biological activities. Dittrichia viscosa (L.) Greuter, a plant species widespread in the Mediterranean region, represents a valuable source of natural bioactive compounds with potential applications in different fields [1]. In particular, five previously undescribed bi- and tricyclic sesquiterpene lactones, inuloxins A–E (Fig. 1), and the known α-costic acid were isolated together from the aerial parts of D. viscosa [2-3]. The structures of these compounds were established by spectroscopic and chemical methods, while their abso-lute configuration was assigned by chiroptical and computational methods. Inuloxins A-E already showed interesting biological properties such as phytotoxic, acaricidal, and antileishmanial activities, suggesting their potential use in diverse applications [4]. This study aimed to evaluate their anti-proliferative potential in vitro and identify their potential molecular targets in silico through network pharmacology and molecular dynamic simulation approaches, uncovering insights into their mech-anisms of action and therapeutic potential. Furthermore, a new protocol for the efficient purification of bioactive compounds from D. viscosa has been introduced. Specifically, a solid-phase extraction (SPE) technique has been employed, reducing both the number of purification steps and the reliance on organic solvents.