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New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons

Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ)...

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Autores principales: Hernández, Ángela P., Chamorro, Pablo, Rodríguez, Mª Lucena, Miguel del Corral, José M., García, Pablo A., Francesch, Andrés, San Feliciano, Arturo, Castro, Mª Ángeles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831060/
https://www.ncbi.nlm.nih.gov/pubmed/33477484
http://dx.doi.org/10.3390/molecules26020474
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author Hernández, Ángela P.
Chamorro, Pablo
Rodríguez, Mª Lucena
Miguel del Corral, José M.
García, Pablo A.
Francesch, Andrés
San Feliciano, Arturo
Castro, Mª Ángeles
author_facet Hernández, Ángela P.
Chamorro, Pablo
Rodríguez, Mª Lucena
Miguel del Corral, José M.
García, Pablo A.
Francesch, Andrés
San Feliciano, Arturo
Castro, Mª Ángeles
author_sort Hernández, Ángela P.
collection PubMed
description Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI(50) values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI(50) at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.
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spelling pubmed-78310602021-01-26 New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons Hernández, Ángela P. Chamorro, Pablo Rodríguez, Mª Lucena Miguel del Corral, José M. García, Pablo A. Francesch, Andrés San Feliciano, Arturo Castro, Mª Ángeles Molecules Article Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI(50) values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI(50) at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated. MDPI 2021-01-18 /pmc/articles/PMC7831060/ /pubmed/33477484 http://dx.doi.org/10.3390/molecules26020474 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hernández, Ángela P.
Chamorro, Pablo
Rodríguez, Mª Lucena
Miguel del Corral, José M.
García, Pablo A.
Francesch, Andrés
San Feliciano, Arturo
Castro, Mª Ángeles
New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title_full New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title_fullStr New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title_full_unstemmed New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title_short New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
title_sort new antineoplastic naphthohydroquinones attached to labdane and rearranged diterpene skeletons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831060/
https://www.ncbi.nlm.nih.gov/pubmed/33477484
http://dx.doi.org/10.3390/molecules26020474
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