withalongolide a triacetate

Withalongolide A triacetate is a semisynthetic acetylated derivative of withalongolide A, a withanolide originally isolated from the plant Physalis longifolia. Withalongolides are C28 steroidal lactones in the Solanaceae family, structurally related to withaferin A. Withalongolide A triacetate (WGA-TA) has demonstrated potent cytotoxic and antiproliferative activity against various cancer cell lines, including head and neck squamous cell carcinoma (HNSCC), melanoma, and adrenocortical carcinoma. Mechanistically, WGA-TA disrupts the heterochaperone function of Hsp90 by targeting its interaction with the cochaperone cdc37, resulting in inhibition of Hsp90 client proteins, induction of apoptosis, and suppression of signaling pathways including PI3K/Akt/mTOR. This compound has enhanced cytotoxicity and selectivity compared to its parent, particularly in the nanomolar range against melanoma cells. WGA-TA also induces oxidative stress response in tumor cells. Preclinical development is limited by low aqueous solubility[1][3][5][12].

Other names

withalongolide a 4,19,27-triacetate