RESUMEN
Seven new (1-7) and seven previously reported (8-14) halogenated metabolites were isolated from the organic extract of the Brazilian red alga Laurencia catarinensis. The structure elucidation and the assignment of the relative configurations of the new natural products were based on detailed NMR and MS spectroscopic analyses, whereas the structure of metabolite 6 was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of metabolite 1 was determined using the modified Mosher's method. The in vitro cytotoxicity of compounds 1-14 was evaluated against HT29, MCF7, and A431 cell lines.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Hidrocarburos Halogenados/aislamiento & purificación , Hidrocarburos Halogenados/farmacología , Laurencia/química , Antineoplásicos/química , Brasil , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HT29 , Humanos , Hidrocarburos Halogenados/química , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin and deacetylhectochlorin. The recently reported depsipeptide carriebowmide (5) was also present in the extract and isolated as its sulfone artifact (6). Compounds 1-4 were identified by spectroscopic methods. The configurations of the amino acid residues of 3, 4, and 6 were determined by LC-MS analyses of diastereomeric derivatives of the acid hydrolysates (advanced Marfey's method). Based on the configurational analysis of 6, in direct comparison with authentic carriebowmide (5), a minor structural revision of 5 is proposed. Compounds 1 and 2 displayed marginal activity against the beet armyworm (Spodoptera exigua). Compounds 1-4 and 6 were assessed for general cell toxicity in human embryonic kidney (HEK293) cells. Only itralamide B (4) displayed significant cytotoxicity, showing an IC(50) value of 6 +/- 1 muM.
Asunto(s)
Amidas , Depsipéptidos/aislamiento & purificación , Ácidos Grasos Insaturados/aislamiento & purificación , Hidrocarburos Halogenados/aislamiento & purificación , Animales , Cianobacterias/química , Depsipéptidos/química , Depsipéptidos/farmacología , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/farmacología , Femenino , Grenada , Humanos , Hidrocarburos Halogenados/química , Hidrocarburos Halogenados/farmacología , Riñón/citología , Riñón/efectos de los fármacos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Spodoptera/efectos de los fármacosRESUMEN
Field collections of the red macroalgae Ochtodes secundiramea and Portieria hornemannii exhibit site-to-site variations in halogenated monoterpene (HMT) content. In contrast, microplantlets of O. secundiramea and P. hornemannii established through cell and tissue culture techniques had remarkably similar HMT profiles when cultivated in a photobioreactor under identical, controlled conditions. Both algae shared Apakaochtodene B (6) as the only cyclic HMT, 10E-bromomyrcene (3) and 10E-bromo-3-chloro-alpha-myrcene (4) as the dominant acyclic HMTs, and myrcene (1) as their common precursor. Furthermore, HMT yields were comparable between organisms (0.9-1.3 micromol/g dry mass of 6; 3.4-4.4 micromol/g of 3). P. hornemannii microplantlets also contained 7-chloromyrcene (9) as the dominant compound (37-73 micromol/g), suggesting additional chlorination capacity. Proposed pathways for HMT biosynthesis shared by P. hornemannii and O. secundiramea microplantlets possessed two common manifolds: (a) bromonium ion (Br(+))-catalyzed cyclization of 1, followed by chlorination to yield 6; (b) Markovnikov addition of Br(+) at Delta(6,10) of 1 to yield 3 with a marked selectivity (>50:1) for the E isomer, followed by chlorination of 3 to 4. This study demonstrated that bioreactor tissue culture is a new venue for bioprospecting and production of natural compounds from marine macroalgae under a controlled environment.
Asunto(s)
Hidrocarburos Halogenados/aislamiento & purificación , Monoterpenos/aislamiento & purificación , Rhodophyta/química , Catálisis , Ciclización , Cromatografía de Gases y Espectrometría de Masas , Guam , Hidrocarburos Halogenados/química , Hidrocarburos Halogenados/farmacología , Estructura Molecular , Monoterpenos/química , Resonancia Magnética Nuclear Biomolecular , EstereoisomerismoRESUMEN
Three new tetrahydrofuran derivatives, marine monoterpenes, with an unusual chlorobromo vinyl functional group, have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and molecular mechanics (MM2) calculations. These compounds are related to pantofuranoids isolated from the antarctic Pantoneura plocamioides, which strongly suggests a close relationship between these species.