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Development of a Red-Light-Controllable Nitric Oxide Releaser to Control Smooth Muscle Relaxation in Vivo
ACS Chemical Biology ( IF 4 ) Pub Date : 2020-11-09 , DOI: 10.1021/acschembio.0c00601
Naoya Ieda 1 , Yuji Hotta 1 , Ayaka Yamauchi 1 , Atsushi Nishikawa 1 , Takahiro Sasamori 2 , Daisuke Saitoh 1 , Mitsuyasu Kawaguchi 1 , Kazunori Kimura 1 , Hidehiko Nakagawa 1
Affiliation  

We designed and synthesized a novel Si-rhodamine derivative, NORD-1, as a red-light-controllable nitric oxide (NO) releaser, on the basis of photoredox parameter analysis. Red-light-responsive NO release from NORD-1 was confirmed by ESR spin trapping and quantified with an NO electrode and by means of Griess assay. The NO release cross section (ε656 nm·ΦNO) of NORD-1 was calculated to be 3.65 × 102, which is larger than that of a previously reported yellowish-green-light-controllable NO releaser, NO-Rosa5. The photoresponsiveness of NO release from NORD-1 was precise and efficient enough to induce vasodilation ex vivo under Magnus test conditions. Finally, we showed that intracavernous pressure (ICP) could be controlled in rats in vivo with the combination of NORD-1 and a red-light source without increasing systemic blood pressure, which is a serious side effect of usual NO releasers, such as nitroglycerin and isopentyl nitrite. NORD-1 is expected to be a useful chemical tool for NO research, as well as a candidate agent to control the circulatory system.

中文翻译:

红光可控一氧化氮释放剂的开发,以控制体内平滑肌松弛

在光氧化还原参数分析的基础上,我们设计并合成了一种新型的罗丹明衍生物NORD-1,作为可控红光的一氧化氮(NO)释放剂。通过ESR自旋阱确认NORD-1发出的红光响应NO释放,并用NO电极和Griess分析进行定量。的NO释放的横截面(ε 656纳米·Φ NO)NORD-1的经计算为3.65×10 2,其比的较大先前报道的黄绿色光可控NO释放器,NO-Rosa5。NORD-1释放NO的光反应性足够精确和有效,足以在Magnus测试条件下诱导离体血管舒张。最后,我们表明可以控制大鼠的海绵体内压(ICP)在体内结合使用NORD-1和红光源而不增加全身血压,这是常见的NO释放剂(如硝酸甘油和亚硝酸异戊酯)的严重副作用。NORD-1有望成为NO研究的有用化学工具,同时也是控制循环系统的候选药物。
更新日期:2020-11-21
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