Chromanone and chromone scaffolds in cancer and metabolic disorders: advances in synthesis, SAR, and developability (2020-2026).

Chromanone and chromone are related benzopyran-based scaffolds that offer multiple opportunities for structural modification and medicinal chemistry. This review summarizes studies published from 2020 to 2026 on the synthesis, structure-activity relationships, biological activities, and developability of these compounds in cancer and metabolic disorders. Recent synthetic approaches have enabled the modification of the heterocyclic ring, fused benzene ring, and carbonyl region, as well as the preparation of hybrid, fused, and spiro derivatives of these compounds. In anticancer research, these compounds have demonstrated antiproliferative, pro-apoptotic, cell cycle-modulating, and signaling-related effects. In metabolic disorders, the reported activities of these compounds include the inhibition of carbohydrate-digesting enzymes, improvement of insulin signaling, suppression of hepatic glucose production, and regulation of lipid metabolism. The review also evaluated the strength of the available evidence, noting that many studies remain limited to docking, isolated enzyme assays, or cell-based screening. The available information on physicochemical properties, pharmacokinetics, metabolism, safety, and in vivo efficacy is comparatively limited. Future research should prioritize standardized biological evaluations, robust mechanistic validations, and integrated optimization of potency, selectivity, safety, and pharmacokinetic properties to facilitate the translational development of chromanone- and chromone-based compounds.