Semisynthesis of Dolabellane Diterpenes: Oxygenated Analogues with Increased Activity against Zika and Chikungunya Viruses.
J Nat Prod
; 84(4): 1373-1384, 2021 04 23.
Article
em En
| MEDLINE
| ID: mdl-33822611
Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone (1) and (1R,7R,8R,11S)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (2), isolated from Eunicea genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC50) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound 9 showed an EC50 = 0.92 ± 0.08 µM and SI = 820 against ZIKV.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus Chikungunya
/
Antozoários
/
Diterpenos
/
Zika virus
Limite:
Animals
País/Região como assunto:
America do sul
/
Colombia
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Colômbia
País de publicação:
Estados Unidos