Phytochemistry and Multitarget Anticancer Mechanisms of the Genus Asphodelus: Structure–Activity Relationships and Translational Perspectives

Cancer remains a major global health burden, and the limitations of conventional chemotherapy, including multidrug resistance, systemic toxicity, and limited selectivity, continue to drive the search for novel bioactive scaffolds. Natural products represent a cornerstone of anticancer drug discovery, providing structurally diverse templates with multitarget biological activities. The genus Asphodelus (Asphodelaceae), widely distributed in the Mediterranean region, has emerged as a promising yet underexplored source of bioactive secondary metabolites, particularly anthraquinones, bianthrones, and unique hydroxyanthraquinone derivatives such as asphodelin. This review critically integrates current knowledge on the phytochemical composition, structure–activity relationships (SAR), and anticancer properties of Asphodelus species. Special emphasis is placed on anthraquinone derivatives as principal cytotoxic constituents, highlighting the structural determinants influencing DNA interaction, topoisomerase inhibition, reactive oxygen species modulation, apoptosis induction, and cell cycle arrest. Comparative analysis with clinically approved anthraquinone-based chemotherapeutics underscores both structural convergence and pharmacological divergence, particularly regarding glycosylation patterns and pharmacokinetic behavior. Toxicity and selectivity profiles are systematically evaluated, revealing that root-derived extracts generally exhibit higher cytotoxic potency but may present reduced selectivity toward normal cells. In contrast, glycosylated derivatives and flavonoids display improved safety profiles with moderate antiproliferative effects. Key translational challenges, including bioavailability, standardization, and insufficient in vivo validation, are discussed within a drug development framework. Collectively, the evidence positions Asphodelus-derived anthraquinones as promising scaffolds for anticancer lead optimization, while underscoring the necessity for rigorous pharmacological and translational investigations.

کلیدواژه ها:

Asphodelus ، Anthraquinones ، Structure&ndash ، activity relationships ، multitarget anticancer mechanisms ، translational pharmacology ، Selectivity index