ABSTRACT
Four different types of marine natural compounds isolated from tunicates were found to inhibit human aldose reductase. They all are characterized by a heterocyclic system, and at least two phenolic groups are present in the structure. Two of the compounds tested showed an inhibitory potency 5/6-fold higher than that of the known AR inhibitor sorbinil. One notable structural feature of these active compounds is the lack of either the carboxylic acid or the spiro-hydantoin commonly present in the principal classes of currently used inhibitors.
Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Biological Products/isolation & purification , Imidazolidines/isolation & purification , Naphthalenes/isolation & purification , Quinazolines/isolation & purification , Rhodanine/analogs & derivatives , Thiazolidines/isolation & purification , Animals , Biological Products/chemistry , Biological Products/pharmacology , Humans , Imidazolidines/chemistry , Imidazolidines/pharmacology , Marine Biology , Naphthalenes/chemistry , Naphthalenes/pharmacology , Quinazolines/chemistry , Quinazolines/pharmacology , Rhodanine/chemistry , Rhodanine/isolation & purification , Rhodanine/pharmacology , Thiazolidines/chemistry , Thiazolidines/pharmacology , Urochordata/chemistryABSTRACT
The chemical study of the ascidian Aplidium haouarianum has led to the isolation of the new metabolites haouamines A (1) and B (2) which belong to a novel class of alkaloids. The structure of 1 was established by interpretation of its spectroscopic data and those of the N-methyl derivative 3, and confirmed by X-ray crystallographic analysis. The structure of 2 was deduced by spectroscopic study of its peracetyl derivative 2a. In solution each haouamine exists as an unseparable mixture of two interconverting isomers derived by the presence of a highly strained 3-aza-[7]-paracyclophane moiety in their structures. Compound 1 exhibits a selective cytotoxic activity against the HT-29 human colon carcinoma cell line.
Subject(s)
Alkaloids/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Urochordata/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Colonic Neoplasms , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Endothelium/drug effects , Hawaii , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Inhibitory Concentration 50 , Lung Neoplasms , Male , Mice , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Prostatic Neoplasms , Spain , Tumor Cells, Cultured/drug effectsABSTRACT
The ascidian Aplidium conicum from Tarifa Island contains the four new meroterpenoids conidione (1), conicol (2), 2-[(1'E)-3'-methoxy-3',7'-dimethylocta-1',6'-dienyl]benzene-1,4-diol (3), and conitriol (4) together with five related known compounds (5-9). It is proposed that the nonaromatic compound conidione (1) was derived by cyclization of an intermediate conitriol quinone 11. The structures of the new compounds were elucidated by interpretation of spectral data.