Abstract

Natural products are the important source for the discovery of more potent anti-HIV agents. In this study, six daphnane diterpenoids including three unreported structures were isolated from Trigonostemon lii, which showed significant activities against HIV-1 strains replication in the nanomolar/picomolar range. Meanwhile, these diterpenoids significantly inhibited the fusion of H9/HIV-1 IIIB cells with uninfected C8166 cells, with the EC_50s from 1.06 to 8.73 ng/mL, and did not show any inhibition activities against HIV-1 reverse transcriptase. Moreover, all of the diterpenoids shows significant inhibitions against T20-resistan HIV-1 strains, PNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. The results revealed that the six diterpenoids could be a new type of potential lead candidate as an HIV entry inhibitor, particularly for those infected by T20-resistant variants.

Graphic Abstract

中文翻译：

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三角龙中的达芙烷二萜类化合物及其对HIV-1的抑制作用。

摘要

天然产物是发现更有效的抗HIV药物的重要来源。在这项研究中，从Trigonostemon lii中分离了六个包括三个未报告结构的达芙烷二萜类化合物，这些化合物显示出在纳摩尔/皮摩尔范围内对抗HIV-1菌株复制的显着活性。同时，这些二萜类化合物在EC _50s时显着抑制了H9 / HIV-1 IIIB细胞与未感染的C8166细胞的融合。从1.06到8.73 ng / mL，对HIV-1逆转录酶没有抑制作用。此外，所有的二萜类化合物均显示出对T20抗性HIV-1株PNL4-3gp41（36G）V38E，N42S和pNL4-3gp41（36G）V38A，N42T的显着抑制作用。结果表明，六种二萜可能是一种新型潜在的潜在候选候选物，作为HIV进入抑制剂，特别是对于那些感染了T20耐药变体的人。

图形摘要