Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids

The bisabolene-type sesquiterpene bisabolangelone (BBG) can be found in several Angelica species, notably in the seeds of A. silvestris L. from which it was first isolated. BBG can be extracted from those plants or obtained by total synthesis from the monoterpenoid pulegone. Efficient procedures hav...

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Main Author: Christian Bailly
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:European Journal of Medicinal Chemistry Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772417425000330
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author Christian Bailly
author_facet Christian Bailly
author_sort Christian Bailly
collection DOAJ
description The bisabolene-type sesquiterpene bisabolangelone (BBG) can be found in several Angelica species, notably in the seeds of A. silvestris L. from which it was first isolated. BBG can be extracted from those plants or obtained by total synthesis from the monoterpenoid pulegone. Efficient procedures have been proposed to synthesize BBG and derivatives. The present review discusses the origin, bio- and chemical syntheses, and pharmacological properties of BBG. Three main activities have been reported, corresponding to three study periods. Initially, BBG was investigated as an insecticide active against Dermatophagoides (house dust mites) and a few other pest species. Later, the compound revealed marked hypopigmenting and anti-melanogenic activities of potential interest to treat hyperpigmented skin lesions. BBG was shown to competitively inhibit cAMP binding to the regulatory subunit of protein kinase A, to alter the functioning of transcription factors CREB and SOX9 implicated in melanogenesis. More recently, BBG was found to inhibit gastric H+/K+-ATPase, presumably via a direct binding to a site on the luminal surface of the proton pump. This mechanism of action, coupled with the antioxidant and anti-inflammatory effects, stimulated the design of more stable anti-ulcer BBG analogues with a reinforced H+/K+-ATPase inhibitory activity, such as oxime and hydrazone carboxamide derivatives. The better knowledge of the bioactivities and the mechanism of action of BBG should encourage studies of natural products with a similar scaffold, such as paniculides A-D, liginvolones A-D, osterivolones A-D, ashitabaol A and other bisabolenoids. Altogether, the review provides a complete survey of the chemistry and pharmacology of bisabolangelone to shed light on its potential therapeutic interest.
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spelling doaj-art-e4eb0aa5c06f42e8b036621fa98644492025-08-20T03:05:21ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742025-08-011410027710.1016/j.ejmcr.2025.100277Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoidsChristian Bailly0CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER—Cancer Heterogeneity Plasticity and Resistance to Therapies, OncoLille Institut, University of Lille, F-59000, Lille, France; Institute of Pharmaceutical Chemistry Albert Lespagnol (ICPAL), Faculty of Pharmacy, University of Lille, F-59006, Lille, France; OncoWitan, Scientific Consulting Office, F-59290, Lille, France; CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER—Cancer Heterogeneity Plasticity and Resistance to Therapies, OncoLille Institut, University of Lille, F-59000, Lille, France.The bisabolene-type sesquiterpene bisabolangelone (BBG) can be found in several Angelica species, notably in the seeds of A. silvestris L. from which it was first isolated. BBG can be extracted from those plants or obtained by total synthesis from the monoterpenoid pulegone. Efficient procedures have been proposed to synthesize BBG and derivatives. The present review discusses the origin, bio- and chemical syntheses, and pharmacological properties of BBG. Three main activities have been reported, corresponding to three study periods. Initially, BBG was investigated as an insecticide active against Dermatophagoides (house dust mites) and a few other pest species. Later, the compound revealed marked hypopigmenting and anti-melanogenic activities of potential interest to treat hyperpigmented skin lesions. BBG was shown to competitively inhibit cAMP binding to the regulatory subunit of protein kinase A, to alter the functioning of transcription factors CREB and SOX9 implicated in melanogenesis. More recently, BBG was found to inhibit gastric H+/K+-ATPase, presumably via a direct binding to a site on the luminal surface of the proton pump. This mechanism of action, coupled with the antioxidant and anti-inflammatory effects, stimulated the design of more stable anti-ulcer BBG analogues with a reinforced H+/K+-ATPase inhibitory activity, such as oxime and hydrazone carboxamide derivatives. The better knowledge of the bioactivities and the mechanism of action of BBG should encourage studies of natural products with a similar scaffold, such as paniculides A-D, liginvolones A-D, osterivolones A-D, ashitabaol A and other bisabolenoids. Altogether, the review provides a complete survey of the chemistry and pharmacology of bisabolangelone to shed light on its potential therapeutic interest.http://www.sciencedirect.com/science/article/pii/S2772417425000330BisabolangeloneBisabolenoidsSesquiterpeneAnti-ulcerAnti-melanogenicInsecticide
spellingShingle Christian Bailly
Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
European Journal of Medicinal Chemistry Reports
Bisabolangelone
Bisabolenoids
Sesquiterpene
Anti-ulcer
Anti-melanogenic
Insecticide
title Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
title_full Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
title_fullStr Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
title_full_unstemmed Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
title_short Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids
title_sort isolation synthesis mechanism of action and pharmacological activities of bisabolangelone and related bisabolenoids
topic Bisabolangelone
Bisabolenoids
Sesquiterpene
Anti-ulcer
Anti-melanogenic
Insecticide
url http://www.sciencedirect.com/science/article/pii/S2772417425000330
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