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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8467382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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