School of Chinese Medicine, Hong Kong Baptist University , Kowloon, Hong Kong SAR, People's Republic of China.
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago , 835 South Wolcott Avenue, Chicago, Illinois 60612, United States.
J Nat Prod. 2017 Jun 23;80(6):1798-1807. doi: 10.1021/acs.jnatprod.7b00004. Epub 2017 Jun 14.
Justicia gendarussa, a medicinal plant collected in Vietnam, was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant extracts. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A (1). Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drug AZT. Patentiflorin A and two congeners were synthesized, de novo, as an efficient strategy for resupply as well as for further structural modification of the anti-HIV ANL glycosides in the search for drug leads. Subsequently, it was determined that the presence of a quinovopyranosyloxy group in the structure is likely essential to retain the high degree of anti-HIV activity of this type of compounds. Patentiflorin A was further investigated against the HIV-1 gene expression of the R/U5 and U5/gag transcripts, and the data showed that the compound acts as a potential inhibitor of HIV-1 reverse transcription. Importantly, the compound displayed potent inhibitory activity against drug-resistant HIV-1 isolates of both the nucleotide analogue (AZT) and non-nucleotide analogue (nevaripine). Thus, the ANL glycosides have the potential to be developed as novel anti-HIV drugs.
越南产药用植物黄葵（Justicia gendarussa），经超过 4500 种植物提取物评估，被鉴定为抗 HIV-1 的有效先导化合物。该植物茎和根提取物经生物活性导向分离，得到一个抗 HIV 的芳基萘木脂素（arylnaphtalene lignan，ANL）糖苷，名为补骨脂定 A（patentiflorin A，1）。该化合物对 M 和 T 嗜性 HIV-1 分离株的评估表明，其抑制效果明显高于临床使用的抗 HIV 药物 AZT。通过从头合成专利紫堇定 A 及其两个同系物，为抗 HIV 的 ANL 糖苷类药物的供应以及进一步的结构修饰提供了有效的策略，以寻找药物先导化合物。随后确定，结构中存在喹诺吡喃糖氧基对于保持此类化合物的高抗 HIV 活性可能是必要的。专利紫堇定 A 进一步研究了其对 R/U5 和 U5/gag 转录物的 HIV-1 基因表达的影响，结果表明该化合物是 HIV-1 逆转录的潜在抑制剂。重要的是，该化合物对核苷酸类似物（AZT）和非核苷酸类似物（nevaripine）耐药的 HIV-1 分离株均显示出很强的抑制活性。因此，ANL 糖苷类化合物具有开发为新型抗 HIV 药物的潜力。
