کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10587282 | 981426 | 2013 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels
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کلمات کلیدی
mitoKATP channelDCVCTMSMitochondrial ATP-sensitive potassium channelKirNHSDCCHOBttetramethylsilaneN-hydroxysuccinimideDMSO - DMSON,N′-dicyclohexylcarbodiimide - N، N'-dicyclohexylcarbodiimideAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPsur - برinwardly rectifying potassium channel - درون کانال پتاسیم اصلاح شده استdiazoxide - دیازوکسیدDimethylsulfoxide - دیمتیل سولفواکسیدMitochondria - میتوکندریاhydroxybenzotriazole - هیدروکسی بنزوتریازولATP-sensitive potassium channels - کانال های پتاسیم حساس به ATPsulfonylurea receptor - گیرنده سولفونیل اوره
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels](/preview/png/10587282.png)
چکیده انگلیسی
The present work aims at identifying new ion channel modulators able to target mitochondrial ATP-sensitive potassium channels (mitoKATP channels). An innovative approach should consist in fixing a cationic and hydrophobic triphenylphosphonium fragment on the structure of known KATP channel openers. Such phosphonium salts are expected to cross the biological membranes and to accumulate into mitochondria.Previous works revealed that the presence of an (R)-1-hydroxy-2-propylamino chain at the 3-position of 4H-1,2,4-benzothiadiazine 1,1-dioxides KATP channel openers increased, in most cases, the selectivity towards the pancreatic-type (SUR1/Kir6.2) KATP channel. In order to target cardiac mitoKATP channels, we decided to introduce a triphenylphosphonium group through an ester link on the SUR1-selective (R)-7-chloro-3-(1-hydroxy-2-propyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide. The new compounds were found to preserve an inhibitory activity on insulin secretion (SUR1-type KATP channel openers) while no clear demonstration of an impact on mitochondria from cardiomyocytes (measurement of oxygen consumption, respiratory parameters and ATP production on H9C2 cells) was observed. However, the most active (inhibition of insulin release) compound 17 was found to penetrate the cardiac cells and to reach mitochondria.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 21, 1 November 2013, Pages 5878-5881
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 21, 1 November 2013, Pages 5878-5881
نویسندگان
Céline Constant-Urban, Mounia Charif, Eric Goffin, Jean-Claude Van Heugen, Benaïssa Elmoualij, Patrice Chiap, Ange Mouithys-Mickalad, Didier Serteyn, Philippe Lebrun, Bernard Pirotte, Pascal De Tullio,