Neolignans as emerging anticancer leads: Isolation, chemical diversity, structure-activity relationships

Many therapeutic plants contain structurally varied natural phenylpropanoid dimers called neolignans, which are biosynthesized via non-8,8' oxidative coupling routes. They are attractive candidates for anticancer drug development because of their chemical diversity, multitarget pharmacological activity, and ability to alter neoplastic pathways. This study compiles recent developments in the isolation, classification, biosynthesis, morphological diversity, structure-activity relationships (SAR), mechanism of action, and formulation techniques of anticancer neolignans. Using Google Scholar, Science Direct, Web of Science, and Bentham Science databases, a comprehensive literature search was carried out in accordance with PRISMA 2020 principles, encompassing literature accessible up to June 2026. The qualitative analysis includes 179 peer-reviewed studies based on predetermined criteria. For isolation, solvent extraction and chromatographic methods were frequently employed, and structural characterisation was made easier by NMR, HPLC, HRMS, and IR. Significant anticancer action has been demonstrated by various neolignan derivatives; modifications such as fluorination, methoxylation, heterocyclic incorporation, and hybridization improved potency and selectivity. Neolignans exert anticancer effects through apoptosis, cell-cycle arrest, autophagy, and regulation of the MAPK, Wnt/β-catenin, NF-κB, and PI3K/Akt/mTOR pathways. Micelles, liposomes, and nanoparticles are some examples of Nano carrier-based formulations that further enhance solubility, bioavailability, and antitumor effectiveness. All things considered, neolignans are potential natural product-derived anticancer leads; rational SAR-guided optimization, sophisticated delivery methods, and computational drug development may speed up their clinical translation.