title: First enantiospecific syntheses of marine merosesquiterpenes neopetrosiquinones a and B: evaluation of biological activity.
abstract: The first enantiospecific syntheses of neopetrosiquinones A (6) and B (7), two merosesquiterpenes isolated from the deep-water sponge Neopetrosia cf. proxima, from the labdane diterpene trans-communic acid (10) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen-DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (7) and of the synthetic intermediates 8 and 9 against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound 9 (IC50 = 4.1 μM), which was twice as active as natural compound 7 (IC50 = 8.3 μM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents.
authors.affiliation: †Laboratoire de Chimie Organique Appliquée, Département de Chimie, Faculté des Sciences, Université Abdelmalek Essaâdi, Tetouan, Morocco.
authors.forename: Ikram
authors.initials: I
authors.lastname: Chayboun
authors.affiliation: †Laboratoire de Chimie Organique Appliquée, Département de Chimie, Faculté des Sciences, Université Abdelmalek Essaâdi, Tetouan, Morocco.
authors.forename: Ettahir
authors.initials: E
authors.lastname: Boulifa
authors.affiliation: †Laboratoire de Chimie Organique Appliquée, Département de Chimie, Faculté des Sciences, Université Abdelmalek Essaâdi, Tetouan, Morocco.
authors.forename: Ahmed Ibn
authors.initials: AI
authors.lastname: Mansour
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez-Serrano
authors.forename: Esther
authors.initials: E
authors.lastname: Carrasco
authors.forename: Pablo Juan
authors.initials: PJ
authors.lastname: Alvarez
authors.forename: Rachid
authors.initials: R
authors.lastname: Chahboun
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez-Manzaneda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003497:Cyclic N-Oxides; D004224:Diterpenes / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008386:Marine Biology; D008623:Mercaptoethanol / Q000031:analogs & derivatives; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D003497:Cyclic N-Oxides; D004224:Diterpenes; D012717:Sesquiterpenes; C461919:communic acid; C000599573:neopetrosiquinone A; C000599574:neopetrosiquinone B; D008623:Mercaptoethanol; C040255:SL-mercaptoethanol