Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Tigliane 酯显示出许多生物活性，包括抗 HIV-1 活性。我们在本研究中的目的是为四个系列的 tigliane 型二萜建立结构-抗 HIV 活性关系。我们合成并评估了 29 种新的佛波酯衍生物的抗 HIV 活性和对人类肿瘤细胞系的细胞毒性。其中，三种衍生物，两种佛波醇-13-单酯（5d和5e）和一种佛波醇-12,13-二酯（6a)，显示出显着的抗 HIV 活性。我们发现更好的抗 HIV 活性通常与 C-13 上较短的酰基酯有关。特别是酯侧链有苯环的化合物表现出优异的抗HIV活性和良好的安全性指标。由于其具有高选择性指数的显着抗 HIV 效力，佛波醇 12,13-二肉桂酸酯 ( 6a ) 被选为进一步临床前试验的潜在候选者。