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The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential

Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacoki...

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Autores principales: Nistor, Gabriela, Mioc, Marius, Mioc, Alexandra, Balan-Porcarasu, Mihaela, Racoviceanu, Roxana, Prodea, Alexandra, Milan, Andreea, Ghiulai, Roxana, Semenescu, Alexandra, Dehelean, Cristina, Șoica, Codruța
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697306/
https://www.ncbi.nlm.nih.gov/pubmed/36431906
http://dx.doi.org/10.3390/molecules27227807
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author Nistor, Gabriela
Mioc, Marius
Mioc, Alexandra
Balan-Porcarasu, Mihaela
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Ghiulai, Roxana
Semenescu, Alexandra
Dehelean, Cristina
Șoica, Codruța
author_facet Nistor, Gabriela
Mioc, Marius
Mioc, Alexandra
Balan-Porcarasu, Mihaela
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Ghiulai, Roxana
Semenescu, Alexandra
Dehelean, Cristina
Șoica, Codruța
author_sort Nistor, Gabriela
collection PubMed
description Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacokinetic/pharmacological profile. Betulinic acid is a pentacyclic triterpenic compound that was identified as an anticancer agent whose main advantage consists in its selective activity, which ensures the almost total lack of cytotoxic side effects. Conjugates of betulinic acid with substituted triazoles, scaffolds with significant pharmacological properties, were synthesized and tested as anticancer agents in order to achieve new therapeutic alternatives. The current paper aims to obtain a C30-1,2,4-triazole derivative of betulinic acid simultaneously acetylated at C3 whose biological activity was tested against RPMI melanoma cells. The compound revealed significant cytotoxic effects at the tested concentrations (2, 10 and 50 μΜ) by significantly decreasing the cell viability to 88.3%, 54.7% and 24.5%, respectively, as compared to the control. The compound’s testing in normal HaCaT cells showed a lack of toxicity, which indicates its selective dose-dependent anticancer activity. The investigation of its underlying molecular mechanism revealed an apoptotic effect induced at the mitochondrial level, which was validated through high-resolution respirometry studies.
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spelling pubmed-96973062022-11-26 The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential Nistor, Gabriela Mioc, Marius Mioc, Alexandra Balan-Porcarasu, Mihaela Racoviceanu, Roxana Prodea, Alexandra Milan, Andreea Ghiulai, Roxana Semenescu, Alexandra Dehelean, Cristina Șoica, Codruța Molecules Article Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacokinetic/pharmacological profile. Betulinic acid is a pentacyclic triterpenic compound that was identified as an anticancer agent whose main advantage consists in its selective activity, which ensures the almost total lack of cytotoxic side effects. Conjugates of betulinic acid with substituted triazoles, scaffolds with significant pharmacological properties, were synthesized and tested as anticancer agents in order to achieve new therapeutic alternatives. The current paper aims to obtain a C30-1,2,4-triazole derivative of betulinic acid simultaneously acetylated at C3 whose biological activity was tested against RPMI melanoma cells. The compound revealed significant cytotoxic effects at the tested concentrations (2, 10 and 50 μΜ) by significantly decreasing the cell viability to 88.3%, 54.7% and 24.5%, respectively, as compared to the control. The compound’s testing in normal HaCaT cells showed a lack of toxicity, which indicates its selective dose-dependent anticancer activity. The investigation of its underlying molecular mechanism revealed an apoptotic effect induced at the mitochondrial level, which was validated through high-resolution respirometry studies. MDPI 2022-11-12 /pmc/articles/PMC9697306/ /pubmed/36431906 http://dx.doi.org/10.3390/molecules27227807 Text en © 2022 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
Nistor, Gabriela
Mioc, Marius
Mioc, Alexandra
Balan-Porcarasu, Mihaela
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Ghiulai, Roxana
Semenescu, Alexandra
Dehelean, Cristina
Șoica, Codruța
The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title_full The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title_fullStr The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title_full_unstemmed The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title_short The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
title_sort c30-modulation of betulinic acid using 1,2,4-triazole: a promising strategy for increasing its antimelanoma cytotoxic potential
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697306/
https://www.ncbi.nlm.nih.gov/pubmed/36431906
http://dx.doi.org/10.3390/molecules27227807
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