Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections
文献类型：期刊论文
| 作者 | Li, Baoli2; Ni, Shuaishuai2; Chen, Feifei1; Mao, Fei2; Wei, Hanwen2; Liu, Yifu2; Zhu, Jin2; Lan, Lefu1 ; Li, Jian2
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| 刊名 | ACS INFECTIOUS DISEASES
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| 出版日期 | 2018-03 |
| 卷号 | 4期号:3页码:208-217 |
| 关键词 | Staphylococcus aureus diapophytoene desaturase methicillin-resistant Staphylococcus aureus hERG safety |
| ISSN号 | 2373-8227 |
| DOI | 10.1021/acsinfecdis.7b00259 |
| 文献子类 | Article |
| 英文摘要 | Blocking the biosynthesis process of staphyloxanthin has emerged as a promising antivirulence strategy. Our previous research revealed that diapophytoene desaturase was an attractive and druggable target against infections caused by pigmented Staphylococcus aureus. Benzocycloalkane-derived compounds were effective inhibitors of diapophytoene desaturase but limited by high hERG (human Ether-a-go-go Related Gene) inhibition activity. Here, we identified a new type of benzo-hepta-containing cycloalkane derivative as diapophytoene desaturase inhibitors. Among the fifty-eight analogues, 48 (hERG inhibition activity, half maximal inhibitory concentration, IC50, of 16.1 mu M) and 51 (hERG inhibition activity, IC50 > 40 mu M) were distinguished for effectively inhibiting the pigment production of Staphylococcus aureus Newman and three methicillin-resistant Staphylococcus aureus strains, and the four strains were highly sensitize to hydrogen peroxide killing without a bactericidal growth effect. In an in vivo assay, 48 and 51 displayed a comparable effect with linezolid and vancomycin in livers and hearts in mice against Staphylococcus aureus Newman and a more considerable effect against Mu50 and NRS271 with normal administration. |
| WOS关键词 | RESISTANT STAPHYLOCOCCUS-AUREUS ; VIRULENCE ; BIOSYNTHESIS ; STAPHYLOXANTHIN ; NEUTROPHILS ; EPIDEMIC ; CRTN |
| 资助项目 | National Key R&D Program of China[2017YFB0202600] ; National Natural Science Foundation of China[21672064] ; "Shu Guang" project - Shanghai Municipal Education Commission[00000000] ; "Shu Guang" project - Shanghai Education Development Foundation[14SG28] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy ; Infectious Diseases |
| 语种 | 英语 |
| WOS记录号 | WOS:000427443200001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279865]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Lan, Lefu; Li, Jian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 646 Songtao Rd, Shanghai 201203, Peoples R China 2.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Baoli,Ni, Shuaishuai,Chen, Feifei,et al. Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections[J]. ACS INFECTIOUS DISEASES,2018,4(3):208-217. |
| APA | Li, Baoli.,Ni, Shuaishuai.,Chen, Feifei.,Mao, Fei.,Wei, Hanwen.,...&Li, Jian.(2018).Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections.ACS INFECTIOUS DISEASES,4(3),208-217. |
| MLA | Li, Baoli,et al."Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections".ACS INFECTIOUS DISEASES 4.3(2018):208-217. |
入库方式： OAI收割
来源：上海药物研究所
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