Pyridine-Fused C25 abeo-Steroid Alkaloids from a Fungus: Biomimetic Semisynthesis and Anti-HIV Mechanistic Study
文献类型：期刊论文
| 作者 | Wu, Pei-Qian1; Hu, Meng-Yu2; Zuo, Yu-Die1; Zhou, Wei2; Cai, Dong-Yue1; Zhang, Ren-Chao1; Wang, Qian2; Yue, Jian-Min1; Zhou, Bin1 |
| 刊名 | ORGANIC LETTERS
 |
| 出版日期 | 2026-01-30 |
| 卷号 | 28期号:4页码:1258-1263 |
| ISSN号 | 1523-7060 |
| DOI | 10.1021/acs.orglett.5c04913 |
| 英文摘要 | With the employment of feature-based molecular networking-guided screening of a refined reference library, four unconventional conjugates, pyricitristerols A-D (1-4), pyridine-fused C25 abeo-steroids featuring a novel 6/7/7/6/5-fused framework, were isolated from a plant-sourced fungus Penicillium citrinum YSC-1. To account for the pyridine moiety, a biosynthetical route was proposed and substantiated by a concise four-step biomimetic semisynthesis from readily prepared precursors 5-8, highlighted by a defining gold-catalyzed one-pot condensation that forged the core architecture. Biological evaluation revealed that 1-4 potently inhibit HIV-1 replication (IC50 = 0.9-3.6 mu M), and structure-activity analysis showed that the pyridine moiety served as the core pharmacophore, while C-23/C-24 stereochemistry finely tuned activity. Mechanistic investigations integrating time-of-addition/washout assays and molecular docking simulations demonstrated these compounds as early stage HIV-1 entry inhibitors that target host-cell surface components, potentially including receptors, such as CCR5, with the pyridine core and C-23 hydroxy group directly engaging in specific binding interactions. |
| WOS关键词 | UNUSUAL C25 STEROIDS ; RINGS |
| 资助项目 | Natural Science Foundation of Shanghai Municipality[25ZR1401071] ; National Natural Science Foundation of China[22177122] ; Shanghai Rising-Star Program[24QA2711300] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001665904000001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322691]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Yue, Jian-Min; Zhou, Bin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Fudan Univ, Chinese Acad Med Sci, Shanghai Inst Infect Dis & Biosecur,Sch Basic Med, Key Lab Med Mol Virol,Minist Educ,Natl Hlth Commis, Shanghai 200433, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Pei-Qian,Hu, Meng-Yu,Zuo, Yu-Die,et al. Pyridine-Fused C25 abeo-Steroid Alkaloids from a Fungus: Biomimetic Semisynthesis and Anti-HIV Mechanistic Study[J]. ORGANIC LETTERS,2026,28(4):1258-1263. |
| APA | Wu, Pei-Qian.,Hu, Meng-Yu.,Zuo, Yu-Die.,Zhou, Wei.,Cai, Dong-Yue.,...&Zhou, Bin.(2026).Pyridine-Fused C25 abeo-Steroid Alkaloids from a Fungus: Biomimetic Semisynthesis and Anti-HIV Mechanistic Study.ORGANIC LETTERS,28(4),1258-1263. |
| MLA | Wu, Pei-Qian,et al."Pyridine-Fused C25 abeo-Steroid Alkaloids from a Fungus: Biomimetic Semisynthesis and Anti-HIV Mechanistic Study".ORGANIC LETTERS 28.4(2026):1258-1263. |
入库方式： OAI收割
来源：上海药物研究所
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