Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structure...

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Detalles Bibliográficos
Autores: Taddeo, Vito A., Núñez, Marvin J., Beltrán, Manuela, Castillo, Ulises G., Menjívar, Jenny, Jiménez, Ignacio A., Alcamí, José, Bedoya Del Olmo, Luis Miguel, Bazzocchi, Isabel L.
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/125161
Acceso en línea:https://hdl.handle.net/20.500.14352/125161
Access Level:acceso abierto
Palabra clave:615.32
HIV-1, Withanolides, natural products
Farmacología (Farmacia)
3209.05 Farmacognosia
3209.90 Farmacología Experimental
Descripción
Sumario:The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 μM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.