Integrasone Derivatives Isolated from Lepteutypa sp. KT4162 and Their Anti-HIV-1 Integrase Activity
Integrasone Derivatives Isolated from Lepteutypa sp. KT4162 and Their Anti-HIV-1 Integrase Activity
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从 Lepteutypa sp. 中分离出的 Integrasone 衍生物。
DOI：
10.1021/acs.jnatprod.3c00065
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发表时间：
2023
期刊：
影响因子：
5.1
通讯作者：
Hashimoto Masaru
中科院分区：
文献类型：
--
作者：
Miura Satomi;Ishida Kotaro;Tanaka Kazuaki;Morita Eiji;Hashimoto Masaru
从钩端螺旋体（Lepteutypasp）的培养液中分离得到5个整合素衍生物：整合素C（1）、异整合素C（2）、整合素D1（3）、整合素D2（4）和整合素E（5）。KT 4162无论是传统的NMR分析，也不是DFT（密度泛函理论）为基础的计算辅助化学位移的讨论是不够的，以阐明1，4-epoxydiol部分的相对构型。用计算的nJCH值和HMBC光谱进行联合分析有助于确定相对构型。用电子圆二色性（ECD）光谱分析确定了化合物1 - 5的绝对构型。对这些化合物的生物活性测定表明，化合物2对HIV-1整合酶有较强的抑制作用，且无细胞毒性。
Five integrasone derivatives, integrasone C (1), isointegrasone C (2), integrasone D1 (3), integrasone D2 (4), and integrasone E (5), were isolated from the culture broth ofLepteutypasp. KT4162. Neither conventional NMR analyses nor DFT (density functional theory)-based computationally assisted chemical shift discussions were sufficient to elucidate the relative configuration of the 1,4-epoxydiol moiety. A combined analysis using the calculatednJCHvalues and HMBC spectra was helpful to establish the relative configuration. The absolute configurations of1–5were determined using DFT-based ECD (electronic circular dichroism) spectral analysis. Biological assays of these compounds revealed that2potently inhibits HIV-1 integrase without cytotoxicity.