Triazole-based structural modification of plant- and fungal-derived natural products: recent advances in bioactivity...

Plant- and fungal-derived natural products remain important sources of bioactive scaffolds for pharmacological research and lead discovery. However, their further development may be limited by poor aqueous solubility, metabolic instability, moderate potency, low bioavailability, or insufficient target selectivity. Triazole-based structural modification, particularly 1,2,3-triazole formation via click chemistry, provides a versatile strategy for diversifying natural-product scaffolds and optimizing their biological properties. This review critically summarizes studies published from June 2021 to April 2026 on the design, synthesis, biological activities, and structure-activity relationships of triazole-modified natural products and related scaffolds derived mainly from plants and fungi. Representative terpenoids, steroids, flavonoids, coumarins, chalcones, curcuminoids, lignans, alkaloids, phenolics, and fungal metabolites are comparatively discussed across anticancer, antimicrobial, anti-inflammatory, antiviral, antiparasitic, neuroprotective and alzheimer's disease-related activities, antidiabetic, and phytotoxic activities. Particular emphasis is placed on the influence of the position of triazole incorporation, substitution patterns, linker characteristics, and parent scaffolds on biological activity, together with comparisons with parent compounds and positive controls where available. Overall, triazole incorporation frequently improved biological activity within individual derivative series; however, direct cross-study comparisons remain limited by differences in biological models and assay conditions. Moreover, most reported compounds remain at the in vitro stage, with limited target validation, in vivo efficacy, pharmacokinetic, metabolic, and long-term toxicity data. This review provides a critical medicinal-chemistry perspective on recent triazole-modified natural products and highlights structural features and evidence gaps relevant to their further development as bioactive leads.