An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety.
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 s...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5040443?pdf=render |
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author | Armando Antillón Alexander H de Vries Marcel Espinosa-Caballero José Marcos Falcón-González David Flores Romero Javier González-Damián Fabiola Eloísa Jiménez-Montejo Angel León-Buitimea Manuel López-Ortiz Ricardo Magaña Siewert J Marrink Rosmarbel Morales-Nava Xavier Periole Jorge Reyes-Esparza Josué Rodríguez Lozada Tania Minerva Santiago-Angelino María Cristina Vargas González Ignacio Regla Mauricio Carrillo-Tripp Mario Fernández-Zertuche Lourdes Rodríguez-Fragoso Iván Ortega-Blake |
author_facet | Armando Antillón Alexander H de Vries Marcel Espinosa-Caballero José Marcos Falcón-González David Flores Romero Javier González-Damián Fabiola Eloísa Jiménez-Montejo Angel León-Buitimea Manuel López-Ortiz Ricardo Magaña Siewert J Marrink Rosmarbel Morales-Nava Xavier Periole Jorge Reyes-Esparza Josué Rodríguez Lozada Tania Minerva Santiago-Angelino María Cristina Vargas González Ignacio Regla Mauricio Carrillo-Tripp Mario Fernández-Zertuche Lourdes Rodríguez-Fragoso Iván Ortega-Blake |
author_sort | Armando Antillón |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-11T22:53:07Z |
format | Article |
id | doaj.art-55cfd25adb6440f28812f62dbb531ff4 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-11T22:53:07Z |
publishDate | 2016-01-01 |
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series | PLoS ONE |
spelling | doaj.art-55cfd25adb6440f28812f62dbb531ff42022-12-22T00:47:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016217110.1371/journal.pone.0162171An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety.Armando AntillónAlexander H de VriesMarcel Espinosa-CaballeroJosé Marcos Falcón-GonzálezDavid Flores RomeroJavier González-DamiánFabiola Eloísa Jiménez-MontejoAngel León-BuitimeaManuel López-OrtizRicardo MagañaSiewert J MarrinkRosmarbel Morales-NavaXavier PerioleJorge Reyes-EsparzaJosué Rodríguez LozadaTania Minerva Santiago-AngelinoMaría Cristina Vargas GonzálezIgnacio ReglaMauricio Carrillo-TrippMario Fernández-ZertucheLourdes Rodríguez-FragosoIván Ortega-BlakeAmphotericin 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.http://europepmc.org/articles/PMC5040443?pdf=render |
spellingShingle | Armando Antillón Alexander H de Vries Marcel Espinosa-Caballero José Marcos Falcón-González David Flores Romero Javier González-Damián Fabiola Eloísa Jiménez-Montejo Angel León-Buitimea Manuel López-Ortiz Ricardo Magaña Siewert J Marrink Rosmarbel Morales-Nava Xavier Periole Jorge Reyes-Esparza Josué Rodríguez Lozada Tania Minerva Santiago-Angelino María Cristina Vargas González Ignacio Regla Mauricio Carrillo-Tripp Mario Fernández-Zertuche Lourdes Rodríguez-Fragoso Iván Ortega-Blake An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. PLoS ONE |
title | An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. |
title_full | An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. |
title_fullStr | An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. |
title_full_unstemmed | An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. |
title_short | An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. |
title_sort | amphotericin b derivative equally potent to amphotericin b and with increased safety |
url | http://europepmc.org/articles/PMC5040443?pdf=render |
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