title: Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity.
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.
authors.affiliation: Universidad Nacional de Colombia, Facultad de Ciencias, Departamento de Química, Av Cra 30 45-03- Bogotá D.C., Código Postal 111321, Colombia.
authors.forename: Alonso
authors.initials: A
authors.lastname: Pardo-Vargas
authors.affiliation: Universidad Nacional de Colombia, Facultad de Ciencias, Departamento de Química, Av Cra 30 45-03- Bogotá D.C., Código Postal 111321, Colombia.
authors.forename: Freddy A
authors.initials: FA
authors.lastname: Ramos
authors.affiliation: 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.
authors.forename: Claudio Cesar
authors.initials: CC
authors.lastname: Cirne-Santos
authors.affiliation: 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.
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Stephens
authors.affiliation: Instituto de Biología, Universidade Federal Fluminense UFF, Niterói, RJ CEP 24001-970, Brazil.
authors.forename: Izabel Christina Palmer
authors.initials: ICP
authors.lastname: Paixão
authors.affiliation: Instituto de Biología, Universidade Federal Fluminense UFF, Niterói, RJ CEP 24001-970, Brazil.
authors.forename: Valeria Laneuville
authors.initials: VL
authors.lastname: Teixeira
authors.affiliation: Universidad Nacional de Colombia, Facultad de Ciencias, Departamento de Química, Av Cra 30 45-03- Bogotá D.C., Código Postal 111321, Colombia.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Castellanos
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004224:Diterpenes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004224:Diterpenes; C115566:dolabellane; D010100:Oxygen
keywords: Antivirals; Dolabellane diterpenes; Eunicea laciniata; HIV-1; Marine natural products