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An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety

Antillón, A., De Vries, A. H., Espinosa-caballero, M., Falcón-gonzález, J. M., Flores Romero, D., González–damián, J., Jiménez-montejo, F. E., León-buitimea, A., López-ortiz, M., Magaña, R., Marrink, S. J., Morales-nava, R., Periole, X., Reyes-esparza, J., Rodríguez Lozada, J., Santiago-angelino, T. M., Vargas González, M. C., Regla, I., Carrillo-tripp, M., Fernández-zertuche, M., Rodríguez-fragoso, L. & Ortega-blake, I., 28-Sep-2016, In : PLoS ONE. 11, 9, 39 p., e0162171.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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
Amphotericin B is the most potent antimycotic known to date. However due to its large col- lateral 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 contrib- ute 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 selectiv- ity: 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.
Original languageEnglish
Article numbere0162171
Number of pages39
JournalPLoS ONE
Volume11
Issue number9
Publication statusPublished - 28-Sep-2016

    Keywords

  • Amphotericin B, antimycotic, cell membrane, pore formation, mode of action

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