The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products

Antioxidants, such as stilbenes, anthocyanidins, coumarins, tannins and flavonoids, are often based on oxygen-containing redox systems and tend to feature several hydroxyl groups in their chemical structures. From a synthetic perspective, oxygen atoms are prone to bioisosteric replacement with sulfu...

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Main Authors: Muhammad Jawad Nasim, Wesam Ali, Eufrânio N. da Silva Júnior, Rahman Shah Zaib Saleem, Caroline Gaucher, Jadwiga Handzlik, Silvana Pedatella, Claus Jacob
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Sci
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Online Access:https://www.mdpi.com/2413-4155/7/2/74
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author Muhammad Jawad Nasim
Wesam Ali
Eufrânio N. da Silva Júnior
Rahman Shah Zaib Saleem
Caroline Gaucher
Jadwiga Handzlik
Silvana Pedatella
Claus Jacob
author_facet Muhammad Jawad Nasim
Wesam Ali
Eufrânio N. da Silva Júnior
Rahman Shah Zaib Saleem
Caroline Gaucher
Jadwiga Handzlik
Silvana Pedatella
Claus Jacob
author_sort Muhammad Jawad Nasim
collection DOAJ
description Antioxidants, such as stilbenes, anthocyanidins, coumarins, tannins and flavonoids, are often based on oxygen-containing redox systems and tend to feature several hydroxyl groups in their chemical structures. From a synthetic perspective, oxygen atoms are prone to bioisosteric replacement with sulfur and, notably, selenium. The main objective of this narrative literature review is to explore if and how bioisosteric substitution of oxygen with sulfur or selenium can enhance the biological activity of natural products. This replacement boosts the biological activity of the resulting molecules considerably as they now combine the redox and antioxidant properties of the original flavonoids and other natural products with the specific redox behavior of sulfur and selenium. Besides sequestering free radicals and peroxides, they may, for instance, also catalyze the removal of oxidative stressors, capture free metal ions and even provide scope for selenium supplementation. Since these molecules resemble their natural counterparts, they also exhibit considerable selectivity inside the body and a good pharmacokinetic profile. Still, the synthesis of such hybrid molecules integrating sulfur and selenium into flavonoids and other natural products is a challenge and requires innovative synthetic strategies and approaches.
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spelling doaj-art-da20c7e456804931a2bf1e436ed86a382025-08-20T03:27:25ZengMDPI AGSci2413-41552025-06-01727410.3390/sci7020074The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural ProductsMuhammad Jawad Nasim0Wesam Ali1Eufrânio N. da Silva Júnior2Rahman Shah Zaib Saleem3Caroline Gaucher4Jadwiga Handzlik5Silvana Pedatella6Claus Jacob7Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, GermanyDivision of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, GermanyInstitute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, BrazilDepartment of Chemistry and Chemical Engineering, SBA School of Sciences and Engineering, Lahore University of Management Sciences, Lahore 54792, PakistanUniversité de Lorraine, CITHEFOR, F-54000 Nancy, FranceDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, PolandDepartment of Chemical Sciences, University of Napoli Federico II, Via Cintia 4, I-80126 Napoli, ItalyDivision of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, GermanyAntioxidants, such as stilbenes, anthocyanidins, coumarins, tannins and flavonoids, are often based on oxygen-containing redox systems and tend to feature several hydroxyl groups in their chemical structures. From a synthetic perspective, oxygen atoms are prone to bioisosteric replacement with sulfur and, notably, selenium. The main objective of this narrative literature review is to explore if and how bioisosteric substitution of oxygen with sulfur or selenium can enhance the biological activity of natural products. This replacement boosts the biological activity of the resulting molecules considerably as they now combine the redox and antioxidant properties of the original flavonoids and other natural products with the specific redox behavior of sulfur and selenium. Besides sequestering free radicals and peroxides, they may, for instance, also catalyze the removal of oxidative stressors, capture free metal ions and even provide scope for selenium supplementation. Since these molecules resemble their natural counterparts, they also exhibit considerable selectivity inside the body and a good pharmacokinetic profile. Still, the synthesis of such hybrid molecules integrating sulfur and selenium into flavonoids and other natural products is a challenge and requires innovative synthetic strategies and approaches.https://www.mdpi.com/2413-4155/7/2/74bioisosteric replacementcatalysishybrid moleculesreactive selenium species (RSeS)reactive sulfur species (RSS)
spellingShingle Muhammad Jawad Nasim
Wesam Ali
Eufrânio N. da Silva Júnior
Rahman Shah Zaib Saleem
Caroline Gaucher
Jadwiga Handzlik
Silvana Pedatella
Claus Jacob
The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
Sci
bioisosteric replacement
catalysis
hybrid molecules
reactive selenium species (RSeS)
reactive sulfur species (RSS)
title The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
title_full The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
title_fullStr The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
title_full_unstemmed The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
title_short The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
title_sort chalcogen exchange the replacement of oxygen with sulfur and selenium to boost the activity of natural products
topic bioisosteric replacement
catalysis
hybrid molecules
reactive selenium species (RSeS)
reactive sulfur species (RSS)
url https://www.mdpi.com/2413-4155/7/2/74
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