Synthetic derivatives of gibberellin A ₃ with selective antiproliferative activity against human renal carcinoma 786-O cells

Gibberellin A₃ (GA₃, <b>1</b>), a well-known member of the <i>ent</i>-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 <i>α</i>,<i>β</i>-unsaturated ketone unit in gibberellins, five new GA₃-based derivatives (<b>2-6</b>) were designed and synthesised. Their antiproliferative activity against five cancer cells was evaluated. Compound <b>4</b> and <b>5</b> with a ketone group at C-3 exhibited selective cytotoxicity against human renal carcinoma 786-O cells. Specifically, compound <b>4</b> displayed the most potent antiproliferative effect on 786-O cells with an IC₅₀ value of 12.93 <i>μ</i>M.