| Autor: |
Taddeo VA; Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife Spain.; Dipartimento di Farmacia, Università degli Studi 'G. d'Annunzio' Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy., Núñez MJ; Laboratorio de Investigación en Productos Naturales, Facultad de Química y Farmacia, Universidad de El Salvador, Final Avenida de Mártires y Héroes del 30 de Julio, San Salvador 1101, El Salvador., Beltrán M; Retrovirus Laboratory, Department of AIDS Immunopathogenesis, National Centre of Microbiology, Instituto de Salud Carlos III, Ctra. Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain., Castillo UG; Laboratorio de Investigación en Productos Naturales, Facultad de Química y Farmacia, Universidad de El Salvador, Final Avenida de Mártires y Héroes del 30 de Julio, San Salvador 1101, El Salvador., Menjívar J; Museo de Historia Natural de El Salvador, Ministerio de Cultura, San Salvador 1101, El Salvador., Jiménez IA; Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife Spain., Alcamí J; Retrovirus Laboratory, Department of AIDS Immunopathogenesis, National Centre of Microbiology, Instituto de Salud Carlos III, Ctra. Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain., Bedoya LM; Retrovirus Laboratory, Department of AIDS Immunopathogenesis, National Centre of Microbiology, Instituto de Salud Carlos III, Ctra. Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain.; Pharmacology, Pharmacognosy and Botany Department, Pharmacy Faculty, Universidad Complutense de Madrid, Pz. Ramón y Cajal s/n, 28040 Madrid, Spain., Bazzocchi IL; Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife Spain. |
| Abstrakt: |
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 IC 50 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. |
