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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5040443?pdf=render
_version_ 1818544795058962432
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
publisher Public Library of Science (PLoS)
record_format Article
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
work_keys_str_mv AT armandoantillon anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT alexanderhdevries anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT marcelespinosacaballero anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT josemarcosfalcongonzalez anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT davidfloresromero anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT javiergonzalezdamian anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT fabiolaeloisajimenezmontejo anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT angelleonbuitimea anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT manuellopezortiz anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ricardomagana anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT siewertjmarrink anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT rosmarbelmoralesnava anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT xavierperiole anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT jorgereyesesparza anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT josuerodriguezlozada anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT taniaminervasantiagoangelino anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mariacristinavargasgonzalez anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ignacioregla anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mauriciocarrillotripp anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mariofernandezzertuche anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT lourdesrodriguezfragoso anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ivanortegablake anamphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT armandoantillon amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT alexanderhdevries amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT marcelespinosacaballero amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT josemarcosfalcongonzalez amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT davidfloresromero amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT javiergonzalezdamian amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT fabiolaeloisajimenezmontejo amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT angelleonbuitimea amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT manuellopezortiz amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ricardomagana amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT siewertjmarrink amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT rosmarbelmoralesnava amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT xavierperiole amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT jorgereyesesparza amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT josuerodriguezlozada amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT taniaminervasantiagoangelino amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mariacristinavargasgonzalez amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ignacioregla amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mauriciocarrillotripp amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT mariofernandezzertuche amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT lourdesrodriguezfragoso amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety
AT ivanortegablake amphotericinbderivativeequallypotenttoamphotericinbandwithincreasedsafety