Synthetic derivatives of gibberellin A3 with selective antiproliferative activity against human renal carcinoma 786-O cells.

Gibberellin A3 (GA3, 1), a well-known member of the ent-kaurene tetracyclic diterpenoid family, exhibits diverse bioactivities. It serves as a lead compound in medicinal chemistry. In this study, inspired by the chemical structure of anticancer vorinostat and the bioactive α,β-unsaturated ketone unit in gibberellins, five new GA3-based derivatives (2-6) were designed and synthesised. Their antiproliferative activity against five cancer cells was evaluated. Compound 4 and 5 with a ketone group at C-3 exhibited selective cytotoxicity against human renal carcinoma 786-O cells. Specifically, compound 4 displayed the most potent antiproliferative effect on 786-O cells with an IC50 value of 12.93 μM.