A multicomponent reaction-based platform opens new avenues in Aryl Hydrocarbon Receptor modulation
A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarbazoles. The conformational behavior of these...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/221704 |
| Acceso en línea: | https://hdl.handle.net/2445/221704 |
| Access Level: | acceso abierto |
| Palabra clave: | Química farmacèutica Síntesi orgànica Compostos heterocíclics Pharmaceutical chemistry Organic synthesis Heterocyclic compounds |
| Sumario: | A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarbazoles. The conformational behavior of these compounds was examined to rationalize their axial chirality. In silico docking and molecular simulations highlighted key features implicated in their binding to AhR. Furthermore, the synthesis of linkable derivatives allowed the direct development of conjugated entities. Reporter gene and target gene expression analyses identified these novel structures as potent noncytotoxic activating AhR ligands, that can be extended to bifunctional molecules. The anti-inflammatory properties of these AhR agonists were assessed in interleukin-13 treated keratinocytes. Altogether, the synergistic research in synthetic and computational chemistry integrated with biological studies opens novel avenues toward understanding the biological roles of AhR and the development of targeted therapeutics. |
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