RESUMO
Chemical investigation of a new species of the deep-water marine sponge Leiodermatium, collected by manned submersible at a depth of 740 feet in Palau, resulted in the isolation of two cytotoxic macrolides, leiodolides A (1) and B (2). The leiodolides represent the first members of a new class of 19-membered ring macrolides, incorporating several unique functional groups including a conjugated oxazole ring, a bromine substituent, and an alpha-hydroxy-alpha-methyl carboxylic acid side-chain terminus. The structures of these new metabolites were established by spectroscopic analysis, chemical modification, and degradation. The relative and absolute stereochemistries at most chiral centers were assigned on detailed interpretation of spectroscopic data, coupled with chemical degradation and application of the modified Mosher ester method. Leiodolide A showed significant cytotoxicity (average GI(50) = 2.0 microM) in the National Cancer Institute's 60 cell line panel with enhanced activity against HL-60 leukemia and OVCAR-3 ovarian cancer cell lines.
Assuntos
Antineoplásicos , Macrolídeos , Oxazóis , Poríferos/química , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Macrolídeos/isolamento & purificação , Macrolídeos/farmacologia , Estrutura Molecular , Oxazóis/isolamento & purificação , Oxazóis/farmacologia , EstereoisomerismoRESUMO
The identification of natural product producer organisms remains a problem for both isolation and natural product classification. A concise screen is developed through fluorescent modification of a set of natural products that offer a common activity. Through real-time multicolor microscopy, the processing, storage, and effects of a natural product are rapidly screened at the level of the strain and individual organism.
Assuntos
Produtos Biológicos/análise , Biotecnologia/métodos , Animais , Produtos Biológicos/biossíntese , Dinoflagellida/metabolismo , Dinoflagellida/ultraestrutura , Corantes Fluorescentes/síntese química , Sensibilidade e EspecificidadeRESUMO
Four beta-carbolines, plakortamines A-D, two cyclic peroxides, epiplakinic acids G and H, and two related gamma-lactones, (2S,4R)- and (2R,4R)-2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactones, were isolated from the deep-water sponge Plakortis nigra from Palau. The structures of the eight new metabolites were elucidated by interpretation of spectroscopic data. Most of the metabolites inhibited the HCT-116 human colon tumor cell line.
