Division of Chronic Viral Diseases, Center for Emerging Virus Research, Korea National Institute of Health, 187 Osongsaengmyeong 2-ro, Cheongju 363951, Korea.
Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Daejeon 34114, Korea.
Molecules. 2022 Aug 2;27(15):4921. doi: 10.3390/molecules27154921.
The heterocyclic indole structure has been shown to be one of the most promising scaffolds, offering various medicinal advantages from its wide range of biological activity. Nonetheless, the significance of 3-oxindole has been less known. In this study, a series of novel 3-oxindole-2-carboxylates were synthesized and their antiviral activity against human immunodeficiency virus-1 (HIV-1) infection was evaluated. Among these, methyl ()-2-(3-chloroallyl)-4,6-dimethyl-one () exhibited the most potent inhibitory effect on HIV-1 infection, with a half-maximal inhibitory concentration (IC) of 0.4578 μM but without severe cytotoxicity (selectivity index (SI) = 111.37). The inhibitory effect of these compounds on HIV-1 infection was concordant with their inhibitory effect on the viral replication cycle. Mode-of-action studies have shown that these prominent derivatives specifically inhibited the Tat-mediated viral transcription on the HIV-1 LTR promoter instead of reverse transcription or integration. Overall, our findings indicate that 3-oxindole derivatives could be useful as a potent scaffold for the development of a new class of anti-HIV-1 agents.
杂环吲哚结构已被证明是最有前途的支架之一，其广泛的生物活性提供了多种医学优势。然而，3-氧代吲哚的重要性却知之甚少。在这项研究中，我们合成了一系列新型的 3-氧代吲哚-2-羧酸酯，并评估了它们对人类免疫缺陷病毒-1（HIV-1）感染的抗病毒活性。在这些化合物中，（）-2-（3-氯烯丙基）-4,6-二甲基-1-（甲氧基）-1H-吲哚-3-羧酸甲酯（）对 HIV-1 感染表现出最强的抑制作用，半数最大抑制浓度（IC）为 0.4578 μM，且没有严重的细胞毒性（选择性指数（SI）=111.37）。这些化合物对 HIV-1 感染的抑制作用与其对病毒复制周期的抑制作用一致。作用机制研究表明，这些显著的衍生物特异性抑制 HIV-1 LTR 启动子上的 Tat 介导的病毒转录，而不是逆转录或整合。总的来说，我们的研究结果表明，3-氧代吲哚衍生物可以作为开发新型抗 HIV-1 药物的有效支架。
