Marine pharmacology: potentialities in the treatment of infectious diseases, osteoporosis and Alzheimer's disease.

Several molecules isolated from various marine organisms (microorganisms, algae, fungi, invertebrates, and vertebrates) are currently under study at an advanced stage of clinical trials, either directly or in the form of analogues deduced from structure-activity relationships. Some of them have already been marketed as drugs. The goal of this article is not to present a complete panorama of marine pharmacology but to show that new models and new mechanisms of action of marine substances bring new solutions for tackling some of the major public health problems of the 21st century. These include: malaria, which assails mainly the southern hemisphere; tuberculosis, an infectious disease once believed to be eliminated but alarmingly increasing, especially among HIV-positive populations; and osteoporosis and Alzheimer's disease, the extension of which are correlated with ageing populations, especially in the developed countries.

Sulfated compounds from marine organisms.

More than 500 sulfated compounds have been isolated from marine organisms so far but most of them originate from two phyla only, Spongia and Echinodermata. The sulfated compounds are presented according to the phyla they have been identified from and to their chemical structures. Biological activities, when available, are also given. Macromolecules have also been included in this review but without structural details.

New unsaturated long-chain fatty acids in the phospholipids from the Axinellida sponges Trikentrion loeve and Pseudaxinella cf. lunaecharta.

In order to identify new structures and especially those involved as biosynthetic intermediates, the fatty acid composition of whole phospholipids from two Senegalese marine sponges from the order Axinellida, Trikentrion loeve and Pseudaxinella cf. lunaecharta, has been investigated by analytical gas chromatography and gas chromatography/mass spectrometry. Several new fatty acids were identified as methyl esters and N-acyl pyrrolidides, namely 16-eicosenoic, 11-tetracosenoic, 5-pentacosenoic, 11-hexacosenoic, 11-octacosenoic, 23-triacontenoic, 17,21-hexacosadienoic, 19,23-octacosadienoic, 9,23-triacontadienoic, 5,9,21-hexacosatrienoic, and 5,9,25-triacontatrienoic. Trikentrion loeve and P. cf. lunaecharta contain fifteen (25.7% of the total acid mixture) and thirteen (30.4%) delta 5,9 fatty acids, respectively. Based on gas chromatography/Fourier transform infrared experiments, the double bonds were assigned the (Z) configuration. Biosynthesis of dienoic and trienoic demospongic acids possessing an n-5 or an n-7 terminal double bond is discussed.

New branched-chain fatty acids from the Senegalese gorgonian Leptogorgia piccola (white and yellow morphs).

Fatty acids from total lipids of the gorgonian Leptogorgia piccola (white and yellow morphs), collected from the same area at two different periods with regard to the average water temperature, were studied. More than fifty fatty acids were identified as methyl esters and N-acyl pyrrolidides by gas chromatography and gas chromatography/mass spectrometry. Three new, branched-chain unsaturated fatty acids were identified in addition to the unusual 7-methyl-6-hexadecenoic acid, namely 10-methyl-6-hexadecenoic, 7,9-dimethyl-6-hexadecenoic, and 10-methyl-6,9-heptadecadienoic acids. Also 6,9-heptadecadienoic acid was identified. The fatty acid patterns of specimens harvested in colder waters were quite different from those harvested in warmer waters in that the former contained high amounts of methylene-interrupted polyunsaturated acids, including tetracosapolyenoic acids, especially 6,9,12,15,18-24:5 (up to 15.8% of the total acid mixture) and 6,9,12,15,18,21-24:6 (up to 5.3%). Arachidonic acid was, nevertheless, a major component in all the fatty acid mixtures studied (13.6-20.5%). Based on gas chromatography/Fourier transform infrared experiments, the double bonds were assigned the (Z) configuration. Several fatty aldehydes and their dimethyl acetals were also detected, of which the most abundant was octadecanal.

Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from Lissoclinum bistratum.

The isolation and characterization is described of four novel cyclic polyethers, bistramides B [2], C [3], D [4], and K [5], which are closely related to the previously reported bistramide A [1] from the New Caledonian urochordata Lissoclinum bistratum. The structures of these metabolites were defined by spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC-N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are less toxic than bistramides A, B, and C and are thereby effective in vivo against NSCLC-N6.

Effects in vitro of sulfated polysaccharide from Schizymenia dubyi (Rhodophyta, Gigartinales) on a non-small-cell bronchopulmonary carcinoma line (NSCLC-N6).

An unusual sulfated heteropolysaccharide containing uronic acids, previously isolated from the red alga Schizymenia dubyi, was studied in vitro for its effect on asynchronous cells of a human non-small-cell-bronchopulmonary carcinoma line (NSCLC-N6). Cell growth appeared to be inhibited in the G1 phase of the cell cycle, and kinetic studies in pretreated cells showed that this growth arrest was irreversible. These events are related to a terminal maturation induction.

New natural 2-acetoxy fatty acids using chemical ionization and electron impact mass spectrometry.

The phospholipids of the sponge Polymastia gleneni contain saturated long chain (C22-30)-acetoxy fatty acids. Their structures were assigned based on chromatographic and spectrometric data as well as comparison with a synthetic sample. The use of capillary gas chromatography combined with chemical ionization and electron impact mass spectrometry was instrumental in the eludication of structures, since only a very small amount of crude lipids was available.

Phospholipid studies of marine organisms: V(1) new α-methoxy acids fromHigginsia tethyoides.

The phospholipids of the demospongeHigginsia tethyoides are shown to have at least 16 long-chain α-methoxy acids, which represent a new class of fatty acids. Among them are the saturated α-methoxy acids containing 19-24 carbon atoms. The monounsaturated compounds are 2-OMe-Δ(17)-24:1, 2-OMe-Δ(18)-25:1, 2-OMeΔ(19)-26:1 and 2-OMe-Δ(21)-28:1. The major diunsatured ones were shown to be 2-OMe-Δ(5, 19)-26:2 and 2-OMe-Δ(7, 21)-28:2. Small amounts of 2-OMe-23∶1, 2-OMe-26∶3; 2-OMe-27∶1 and 2-OMe-28∶3 were also encountered. Structures of the minor monounsaturated compounds were tentatively assigned as 2-methoxy-16-tricosenoic acid and 2-methoxy-20-heptacosenoic acids. The double bonds of the fatty acids show all-cis configuration. Circular dichroism measurements indicate an R-configuration for the α-methoxy acids. The major component of the total phospholipid acid mixture is 5,9,23-triacontatrienoic acid. Possible biosynthetic routes to these unusual phospholipid acids are discussed. The major phospholipids were phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine. The distribution of fatty acids among the phospholipids was also investigated.