A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety
文献类型：期刊论文
| 作者 | Peng, Wen7,8; Qin, Lixiao6; Wang, Tianci7,8; Sun, Yangqian7,8; Li, Zhen3; Lefer, David J.3; Luo, Cheng2 ; Ye, Fei1; Wang, Binghe4,5; Guo, Weiwei6
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2024-09-24 |
| 卷号 | 67期号:19页码:17350-17362 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.4c01254 |
| 通讯作者 | Wang, Binghe(wang@gsu.edu) ; Guo, Weiwei(guoweiwei@cpu.edu.cn) ; Zheng, Yueqin(yzheng@cpu.edu.cn) |
| 英文摘要 | Efforts to synergize hydrogen sulfide (H2S) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel H2S releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of H2S and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release H2S. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models. |
| WOS关键词 | HYDROGEN-SULFIDE ; RELEASE ; DONORS |
| 资助项目 | National Natural Science Foundation of China, China[22107116] ; National Natural Science Foundation of China, China[22377147] ; Natural Science Foundation of Jiangsu Province, China[BK20210415] ; Project of the State Key Laboratory of Natural Medicines, China Pharmaceutical University |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001319867200001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313618]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Binghe; Guo, Weiwei; Zheng, Yueqin |
| 作者单位 | 1.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou 310018, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Ctr Chem Biol,State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Cedars Sinai Med Ctr, Smidt Heart Inst, Dept Cardiac Surg, Los Angeles, CA 90048 USA 4.Georgia State Univ, Ctr Diagnost & Therapeut, Atlanta, GA 30303 USA 5.Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA 6.China Pharmaceut Univ, Dept Chem, Nanjing 211198, Peoples R China 7.China Pharmaceut Univ, Ctr Drug Discovery, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 211198, Peoples R China 8.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 211198, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng, Wen,Qin, Lixiao,Wang, Tianci,et al. A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024,67(19):17350-17362. |
| APA | Peng, Wen.,Qin, Lixiao.,Wang, Tianci.,Sun, Yangqian.,Li, Zhen.,...&Zheng, Yueqin.(2024).A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety.JOURNAL OF MEDICINAL CHEMISTRY,67(19),17350-17362. |
| MLA | Peng, Wen,et al."A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety".JOURNAL OF MEDICINAL CHEMISTRY 67.19(2024):17350-17362. |
入库方式： OAI收割
来源：上海药物研究所
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