两性霉素B
多烯
衍生工具(金融)
药理学
化学
毒性
作用机理
选择性
立体化学
医学
生物化学
生物
体外
抗真菌
微生物学
有机化学
金融经济学
催化作用
经济
作者
Armando Antillón,Alexander H. de Vries,Marcel Espinosa-Caballero,José Marcos Falcón-González,David F. Romero,Javier González–Damián,Fabiola Eloísa Jiménez-Montejo,Ángel León-Buitimea,Manuel López-Ortíz,Ricardo Magaña,Siewert J. Marrink,Rosmarbel Morales‐Nava,Xavier Periole,Jorge Reyes‐Esparza,Josué Rodríguez-Lozada,Tania Minerva Santiago-Angelino,M. Cristina Vargas González,Ignacio Regla,Mauricio Carrillo‐Tripp,Mario Fernández‐Zertuche,Lourdes Rodríguez‐Fragoso,Iván Ortega‐Blake
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2016-09-28
卷期号:11 (9): e0162171-e0162171
被引量:28
标识
DOI:10.1371/journal.pone.0162171
摘要
Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety.
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