From Aryltetralin Anticancer Scaffolds to Host-Directed Bioactivities: A Mechanism-Based Review of Lignans and Neolignans

Lignans and related neolignans are a diverse class of phenolic natural products with broad biological activities and great potential for pharmaceutical applications. This article summarizes representative subclasses of lignans and compares their antitumor and antioxidant properties from a structural and mechanistic perspective. Aryltetrahydronaphthalene lignans, represented by podophyllotoxin and its semi-synthetic derivatives, provide the clearest baseline for their mechanism of action by disrupting microtubules and inhibiting topoisomerase II. Other subclasses, including dibenzylbutyrolactone, arylnaphthalene, dibenzocyclooctadiene, furofuran lignans, glycosides, and bisphenolic neolignans, exhibit anticancer and redox-regulating effects. Future research should focus on linking structural diversity with validated molecular targets, pharmacokinetic properties, and in vivo efficacy to better define their translational potential.