Synthesis and anti-leukemia activity of phorbol 13,20-diesters and phorbol 12,13,20-triesters

Phorbol esters and their derivatives, such as TPA, have been reported potential natural antitumor products, with some derivatives entering clinical research for leukemia treatment. In this study, 16 phorbol were synthesized from phorbol, anti-leukemia activity against Jurkat, HL-60, K562 tested. The results showed that several had activity, 5B demonstrating the strongest cytotoxic cell line (IC 50 = 0.24 ± 0.04 μM). Based on IC values, a structure-activity relationship was established. When substituent contained an aromatic group, esterified long-chain organic acids at three reactive hydroxyl groups (C12-OH, C13-OH, C20-OH) better activity. aryl absent groups, short-chain two Derivatives heterocyclic acids, either tri-substituted or di-substituted, significant decrease in cytotoxicity. mechanism of explored through flow cytometry, which indicated inhibited growth cells by inducing apoptosis, leading to death. Molecular docking data compound PKC δC1B suggested should not be too large, caution taken when substituting C20-OH. Overall, these findings provide valuable insights into design more effective agents, but further is needed confirm safety efficacy settings.