Phytochemical diversity and therapeutic potential of Verbesina metabolites: a critical review of sesquiterpene lactones and translational feasibility.

The global health crisis driven by Antimicrobial Resistance (AMR) necessitates a pivot toward novel therapeutic agents, yet the Asteraceae genus Verbesina remains significantly under-characterized. Despite comprising over 300 species, early assessments indicated that only approximately 10% had been biologically investigated. This review provides a critical synthesis of the pharmacological landscape of Verbesina, focusing on the structural duality of its major specialized metabolites, the Sesquiterpene Lactones (SLs). The review systematically analyzes reported in vitro data, emphasizing high-potency scaffolds such as 6β-cinnamoyloxy-3β,4α-dihydroxyeudesmane (MIC = 3.9 μg/mL) and Verbesindiol (IC50 = 4.0 ± 0.6 μM) against prostate cancer cells. A core focus is placed on the Selectivity Index (SI = IC50/MIC); to address the translational challenge of non-selective toxicity. Notably, an Arbusculin derivative demonstrates a superior SI of up to 88.2, significantly outperforming standard drugs like meglumine antimoniate (SI = 40.0). Furthermore, the review evaluates the molecular mechanisms of action, such as the role of the α-methylene-γ-lactone moiety in alkylating cellular targets, while distinguishing structure-specific effects like mitochondrial uncoupling and respiratory chain inhibition. By bridging ethnopharmacology with modern mechanistic and quantitative data, this review critically assesses the translational potential of Verbesina metabolites, exposes current methodological limitations in the literature, and highlights clear directions for bioassay-guided isolation and chemical optimization as next-generation anti-resistance scaffolds.