Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription

  • J Nat Prod. 2021 Oct 22;84(10):2717-2726. doi: 10.1021/acs.jnatprod.1c00637.
Vito A Taddeo  1  2 ,  Marvin J Núñez  3 ,  Manuela Beltrán  4 ,  Ulises G Castillo  3 ,  Jenny Menjívar  5 ,  Ignacio A Jiménez  1 ,  José Alcamí  4 ,  Luis M Bedoya  4  6 ,  Isabel L Bazzocchi  1
Affiliations
  • 1. 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.
  • 2. Dipartimento di Farmacia, Università degli Studi "G. d'Annunzio" Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • 3. 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.
  • 4. Retrovirus Laboratory, Department of AIDS Immunopathogenesis, National Centre of Microbiology, Instituto de Salud Carlos III, Ctra. Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain.
  • 5. Museo de Historia Natural de El Salvador, Ministerio de Cultura, San Salvador 1101, El Salvador.
  • 6. Pharmacology, Pharmacognosy and Botany Department, Pharmacy Faculty, Universidad Complutense de Madrid, Pz. Ramón y Cajal s/n, 28040 Madrid, Spain.
PMID: 34549952 DOI: 10.1021/acs.jnatprod.1c00637
Abstract

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.