Chemical Duality of Verbesina Metabolites: Sesquiterpene Lactones, Selectivity Index (SI), and Translational Feasibility for Anti-Resistance Drug Discovery

The global health crisis driven by Antimicrobial Resistance (AMR) necessitates an urgent pivot toward novel therapeutic agents, with traditional medicinal plants serving as a critical resource. The Asteraceae genus Verbesina, particularly utilized in Mexican ethnobotany, has garnered scientific attention due to its potent bioactive profile against infection and inflammation. This review provides a comprehensive and critical synthesis of the pharmacological landscape of Verbesina species, focusing specifically on the dual role of its major secondary metabolites, the Sesquiterpene Lactones (SLs), as both cytotoxic and antimicrobial agents. We systematically compile and analyze reported in vitro data, including IC50 values from cancer and non-cancerous cell lines, and MIC values against clinically relevant drug-resistant strains like S. aureus and E. coli. A core focus is placed on establishing the therapeutic index (SI = IC50/MIC) for lead compounds, providing a crucial indicator of drug feasibility. Furthermore, we review the proposed molecular mechanisms of SL action, such as the crucial role of the α-methylene-γ-lactone moiety in alkylating cellular targets, which underpins both their antiproliferative and bactericidal effects. By critically bridging ethnopharmacology with modern mechanistic data, this review validates the translational potential of Verbesina metabolites and highlights clear directions for bioassay-guided isolation and optimization as next-generation anti-resistance scaffolds.