Novel cyclophilin d inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and ca2+ uptake/release
文献类型：期刊论文
| 作者 | Guo, HX; Wang, F; Yu, KQ; Chen, Y; Bai, DL; Chen, KX; Shen, X; Jiang, HL |
| 刊名 | Acta pharmacologica sinica
 |
| 出版日期 | 2005-10-01 |
| 卷号 | 26期号:10页码:1201-1211 |
| 关键词 | Cyclophilin Quinoxalines Surface plasmon resonance Mitochondrial permeability transition Fluorescence titration Inhibitor |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2005.00189.x |
| 通讯作者 | Shen, x(xshen@mail.shcnc.ac.cn) |
| 英文摘要 | Aim: to investigate methods for identifying specific cyclophilin d(cypd) inhibitors derived from quinoxaline, thus developing possible lead compounds to inhibit mitochondrial permeability transition (mpt) pore opening. methods: kinetic analysis of the cypd/inhibitor interaction was quantitatively performed by using surface plasmon resonance (spr) and fluorescence titration (ft) techniques. ic50 values of these inhibitors were determined by ppiase inhibition activity assays. results: all the equilibrium dissociation constants (k-d) of the seven compounds binding to cypd were below 10 mu mol/l. the ic50 values were all consistent with the spr and ft results. compounds gw2, 5, 6, and 7 had high inhibition activities against ca2+-dependent rat liver mitochondrial swelling and ca2+ uptake/release. compound gw5 had binding selectivity for cypd over cypa. conclusion: the agreement between the measured ic50 values and the results of spr and ft suggests that these methods are appropriate and powerful methods for identifying cypd inhibitors. the compounds we screened using these methods (gw1-7) are reasonable cypd inhibitors. its potent ability to inhibit mitochondrial swelling and the binding selectivity of gw5 indicates that gw5 could potentially be used for inhibiting mpt pore opening. |
| WOS关键词 | CIS-TRANS-ISOMERASE ; INTERMEMBRANE JUNCTIONAL COMPLEXES ; PERMEABILITY TRANSITION ; CELL-DEATH ; CRYSTAL-STRUCTURE ; CYCLOSPORINE-A ; CYTOCHROME-C ; BINDING-SITE ; PROTEIN ; APOPTOSIS |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000232346000008 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2377109 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Shen, X |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci,Shanghai Inst Mat Med, State Key Lab Drug Res,Drug Discovery & Design Ct, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, HX,Wang, F,Yu, KQ,et al. Novel cyclophilin d inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and ca2+ uptake/release[J]. Acta pharmacologica sinica,2005,26(10):1201-1211. |
| APA | Guo, HX.,Wang, F.,Yu, KQ.,Chen, Y.,Bai, DL.,...&Jiang, HL.(2005).Novel cyclophilin d inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and ca2+ uptake/release.Acta pharmacologica sinica,26(10),1201-1211. |
| MLA | Guo, HX,et al."Novel cyclophilin d inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and ca2+ uptake/release".Acta pharmacologica sinica 26.10(2005):1201-1211. |
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来源：中国科学院大学
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