Fatty acid derivatives cytotoxicity

A. Kupferberg, G. Teller and P. Behr, Metabolism of 7(5-hydroxycholesterol in astrocyte primary cultures and derived spontaneously transformed cell lines correlation between the esterification on C-3-OH by naturally occurring fatty acids and cytotoxicity, Biochim. Biophys. Acta 1046 (1990) 106-109. 

Fatty acid-derived cychc peroxides are often found in marine sponges of the genus Plakortis the first example was chon-drillin (6). 1,2-Dioxane and 1,2-dioxolane carboxylates were also discovered from Plakortis sponges (9). These cychc oxides show a range of biologic activities, for example, antimicrobial, cytotoxic, and antimalarial activities. 

In addition, a variety of bioactive fatty acid derivatives have been isolated from marine organisms, including glycoceramides (10). Perhaps the most unusual example is a highly chlorinated sulfolipid 7 isolated as a cytotoxic principle from the mussel Mytilus galloprovincialis (10). 

Linear polyacetylenes are found frequently in marine sponges of the order Haplosclerida (11). Although the chain lengths vary from Ci4 to C49, likely they are to be derived from Cie fatty acids. Polyacetylenes show a wide range of bioactivities, including antimicrobial, cytotoxic, antiviral, and enzyme inhibitory. Corticatic acid A (8), which is a C31 polyacetylene carboxyhc acid isolated from Petrosia corticata, is not only antimicrobial, but also it inhibits geranylgeranyltransferase I (12). 

Certain arachidonate aziridines such as 13-(3-pentyl-2-aziridinyl)-5,8,11-trideca-trienoic acid (104) and its methyl ester (105) have been synthesized [123] which are inhibitors of arachidonate epoxygenase [124]. Preparation of the fatty acid aziridines (106-115) has been described [125]. Bis(aziridine) Me cis-9,10 cw-12,13-diepiminooctadecanoate, derived from hnoleic acid, and tris (aziridine) and Me c /s-9,10 c/s-12,13 cfr-15,16-triepimino-octadecanoate, both derived from linolenic acid, showed cytotoxic and antimicrobial activity as well as remarkable antitumor-promoting and useful neuroprotective effects [126]. 

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