HIV-1 Integrase Inhibitor, Dihydroobionin B, and the Investigation of Its Extraordinary Specific Rotation

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2023-08-18 DOI:10.1021/acs.jnatprod.3c00353

Kazuki Hashimoto, Kana Kimura, Kotaro Ishida, Eiji Morita, Kazuaki Tanaka and Masaru Hashimoto*,

{"title":"HIV-1 Integrase Inhibitor, Dihydroobionin B, and the Investigation of Its Extraordinary Specific Rotation","authors":"Kazuki Hashimoto, Kana Kimura, Kotaro Ishida, Eiji Morita, Kazuaki Tanaka and Masaru Hashimoto*, ","doi":"10.1021/acs.jnatprod.3c00353","DOIUrl":null,"url":null,"abstract":"Dihydroobionin B (1), a chiral congener of known obionin B, was isolated from Pseudocoleophoma sp. KT4119, a freshwater fungus collected from a submerged wood block in Kochi Prefecture, Japan, in 2020. The planar structure of 1 was characterized by mass and NMR spectral analysis and confirmed by density functional theory (DFT)-based chemical shift calculations. Its absolute structure was determined by electronic circular dichroism spectral analysis. Notably, 1 exhibited an extraordinarily large specific rotation [[α]20D +1080 (c 0.056, CHCl3)], which was verified by DFT-based specific rotation calculations. However, these calculations indicated that the sign of the specific rotation based on static analysis was insufficient to determine the absolute configuration in this case. Furthermore, Pseudocoleophoma KT4119 produced coleophomapyrones A (2) and B (3) and coleophomaldehyde A (4). While this is the first report of 2 isolated from a natural source, it has also been prepared previously using a synthetic approach. Compound 1 potently inhibited HIV type 1 integrase (IC50 = 0.44 μM) without significant cytotoxicity. Finally, docking experiments were conducted to propose a plausible mechanism for the behavior of 1.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"86 9","pages":"2139–2144"},"PeriodicalIF":3.3000,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jnatprod.3c00353","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Dihydroobionin B (1), a chiral congener of known obionin B, was isolated from Pseudocoleophoma sp. KT4119, a freshwater fungus collected from a submerged wood block in Kochi Prefecture, Japan, in 2020. The planar structure of 1 was characterized by mass and NMR spectral analysis and confirmed by density functional theory (DFT)-based chemical shift calculations. Its absolute structure was determined by electronic circular dichroism spectral analysis. Notably, 1 exhibited an extraordinarily large specific rotation [[α]²⁰_D +1080 (c 0.056, CHCl₃)], which was verified by DFT-based specific rotation calculations. However, these calculations indicated that the sign of the specific rotation based on static analysis was insufficient to determine the absolute configuration in this case. Furthermore, Pseudocoleophoma KT4119 produced coleophomapyrones A (2) and B (3) and coleophomaldehyde A (4). While this is the first report of 2 isolated from a natural source, it has also been prepared previously using a synthetic approach. Compound 1 potently inhibited HIV type 1 integrase (IC₅₀ = 0.44 μM) without significant cytotoxicity. Finally, docking experiments were conducted to propose a plausible mechanism for the behavior of 1.

Abstract Image

查看原文本刊更多论文

HIV-1整合酶抑制剂二氢obionin B及其特异性旋转的研究

二氢obionin B（1）是已知obionin B的手性同源物，于2020年从日本高知县的一个水下木块上采集的淡水真菌Pseudocoleophoma sp.KT4119中分离得到。1的平面结构通过质量和NMR光谱分析进行了表征，并通过基于密度泛函理论（DFT）的化学位移计算得到了证实。通过电子圆二色性光谱分析确定了其绝对结构。值得注意的是，1表现出非常大的比旋[[α]20D+1080（c 0.056，CHCl3）]，这通过基于DFT的比旋计算得到了验证。然而，这些计算表明，在这种情况下，基于静态分析的特定旋转的符号不足以确定绝对配置。此外，假性鞘膜瘤KT4119产生鞘膜酮A（2）和B（3）以及鞘膜醛A（4）。虽然这是第一份从自然来源分离出的2份报告，但它之前也使用了合成方法。化合物1有效地抑制HIV 1型整合酶（IC50＝0.44μM），而没有显著的细胞毒性。最后，进行了对接实验，为1的行为提出了一个合理的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.