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Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B

Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural...

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Autores principales: Szczeblewski, Paweł, Andrałojć, Witold, Polit, Justyna, Żabka, Aneta, Winnicki, Konrad, Laskowski, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467382/
https://www.ncbi.nlm.nih.gov/pubmed/34577003
http://dx.doi.org/10.3390/molecules26185533
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author Szczeblewski, Paweł
Andrałojć, Witold
Polit, Justyna
Żabka, Aneta
Winnicki, Konrad
Laskowski, Tomasz
author_facet Szczeblewski, Paweł
Andrałojć, Witold
Polit, Justyna
Żabka, Aneta
Winnicki, Konrad
Laskowski, Tomasz
author_sort Szczeblewski, Paweł
collection PubMed
description Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural evidence on the stereochemistry of its components has been presented to date. In this contribution, we have conducted detailed, NMR-driven stereochemical studies on mepartricins A and B, aided by molecular dynamics simulations. The absolute configuration of all the stereogenic centers of mepartricin A and B was defined as 3R, 7R, 9R, 11S, 13S, 15R, 17S, 18R, 19S, 21R, 36S, 37R, and 38S, and proposed as 41R. The geometry of the heptaenic chromophore of both compounds has been established as 22E, 24E, 26E, 28Z, 30Z, 32E, and 34E. Our studies on mepartricin ultimately proved that partricins A and B are structurally identical to the previously described main components of the aureofacin complex: gedamycin and vacidin, respectively. The knowledge of the stereochemistry of this drug is a fundamental matter not only in terms of studies on its molecular mode of action, but also for potential derivatization, aiming at improvement of its pharmacological properties.
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spelling pubmed-84673822021-09-27 Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B Szczeblewski, Paweł Andrałojć, Witold Polit, Justyna Żabka, Aneta Winnicki, Konrad Laskowski, Tomasz Molecules Article Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural evidence on the stereochemistry of its components has been presented to date. In this contribution, we have conducted detailed, NMR-driven stereochemical studies on mepartricins A and B, aided by molecular dynamics simulations. The absolute configuration of all the stereogenic centers of mepartricin A and B was defined as 3R, 7R, 9R, 11S, 13S, 15R, 17S, 18R, 19S, 21R, 36S, 37R, and 38S, and proposed as 41R. The geometry of the heptaenic chromophore of both compounds has been established as 22E, 24E, 26E, 28Z, 30Z, 32E, and 34E. Our studies on mepartricin ultimately proved that partricins A and B are structurally identical to the previously described main components of the aureofacin complex: gedamycin and vacidin, respectively. The knowledge of the stereochemistry of this drug is a fundamental matter not only in terms of studies on its molecular mode of action, but also for potential derivatization, aiming at improvement of its pharmacological properties. MDPI 2021-09-12 /pmc/articles/PMC8467382/ /pubmed/34577003 http://dx.doi.org/10.3390/molecules26185533 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szczeblewski, Paweł
Andrałojć, Witold
Polit, Justyna
Żabka, Aneta
Winnicki, Konrad
Laskowski, Tomasz
Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title_full Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title_fullStr Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title_full_unstemmed Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title_short Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
title_sort ipertrofan revisited—the proposal of the complete stereochemistry of mepartricin a and b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467382/
https://www.ncbi.nlm.nih.gov/pubmed/34577003
http://dx.doi.org/10.3390/molecules26185533
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