2. Academic Validation
  3. Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity

Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity

  • Bioorg Med Chem Lett. 2014 Sep 15;24(18):4381-4383. doi: 10.1016/j.bmcl.2014.08.019.
Alonso Pardo-Vargas 1,  Freddy A Ramos 1,  Claudio Cesar Cirne-Santos 2,  Paulo Roberto Stephens 2,  Izabel Christina Palmer Paixão 3,  Valeria Laneuville Teixeira 3,  Leonardo Castellanos 1
Affiliations

Affiliations

  • 1 Universidad Nacional de Colombia, Facultad de Ciencias, Departamento de Química, Av Cra 30 45-03- Bogotá D.C., Código Postal 111321, Colombia.
  • 2 Laboratório de Imunologia Clínica, Departamento de Imunologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Manguinhos, Pavilhão Leônidas Deane/409, Rio de Janeiro, RJ 21045-900, Brazil; Instituto de Biología, Universidade Federal Fluminense UFF, Niterói, RJ CEP 24001-970, Brazil.
  • 3 Instituto de Biología, Universidade Federal Fluminense UFF, Niterói, RJ CEP 24001-970, Brazil.
PMID: 25176328 DOI: 10.1016/j.bmcl.2014.08.019
Abstract

Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these Diterpenoids have strong anti-HIV-1 activity, but there are not data about Antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and β-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high Antiviral activities, along with their low cytotoxicity, make them promissory Antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the Antiviral potency of these diterpeneoids.

Keywords

Antivirals; Dolabellane diterpenes; Eunicea laciniata; HIV-1; Marine natural products.

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