TY - JOUR
T1 - An Amphotericin B derivative equally potent to Amphotericin B and with increased safety
AU - Antillón, Armando
AU - De Vries, Alexander H.
AU - Espinosa-Caballero, Marcel
AU - Falcón-González, José Marcos
AU - Flores Romero, David
AU - González-Damián, Javier
AU - Jiménez-Montejo, Fabiola Eloísa
AU - León-Buitimea, Angel
AU - López-Ortiz, Manuel
AU - Magaña, Ricardo
AU - Marrink, Siewert J.
AU - Morales-Nava, Rosmarbel
AU - Periole, Xavier
AU - Reyes-Esparza, Jorge
AU - Rodríguez Lozada, Josué
AU - Santiago-Angelino, Tania Minerva
AU - Vargas González, María Cristina
AU - Regla, Ignacio
AU - Carrillo-Tripp, Mauricio
AU - Fernández-Zertuche, Mario
AU - Rodríguez-Fragoso, Lourdes
AU - Ortega-Blake, Iván
N1 - Publisher Copyright:
© 2016 Antillón et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991712900&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0162171
DO - 10.1371/journal.pone.0162171
M3 - Artículo
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0162171
ER -