Ma_2026_Bioorg.Chem_183_110643

Plant-derived natural glycosides have been regarded as important factors in plant defense. Their potential as eco-friendly pesticide candidates have attracted increasing interest. This review summarizes progress in research on glycosides with insecticidal, antimicrobial and antiviral activities over the past decades, covering 161 compounds including flavonoid, triterpenoid, steroidal, pregnane, terpenoid, phenolic glycosides, etc., from various plant species. The results indicate that terpenoid including triterpenoid, iridoid, and sesquiterpenoid, along with steroidal glycosides represent the major defense constituents for discovery of novel botanical pesticides. Chemotaxonomic analysis at the family level identifies Ranunculaceae, Fabaceae, Rubiaceae, and Apocynaceae as particularly rich sources of agroactive glycosides. Mechanistic studies suggest that the insecticidal activities of these glycosides are strongly structure-dependent. Flavonoid glycosides mainly act through acetylcholinesterase inhibition, whereas saponins exert toxicity largely by targeting the insect midgut and inhibiting detoxification and digestive enzymes. Chitinase inhibition is also an important mechanism for insecticidal activities of glycosides. For antimicrobial activity, the mechanisms of bioactive glycosides mainly include targeting cell membranes and activating salicylic acid (SA) signaling. Downregulation of viral coat proteins appears to be a major mechanism of antiviral activity for the defense glycosides. By integrating chemical diversity, botanical distribution, bioactivity profiles, and mechanisms of action, this review highlights plant glycosides as a valuable reservoir for green pesticide discovery.