The advancement of structure, bioactivity, mechanism, and synthesis of bufotalin.

Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14-α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact. This review consolidates recent progress on bufotalin's structure, activity, cytotoxic mechanisms, and synthetic methodologies, offering a foundation for further development as an innovative chemotherapy agent.