Extracts and pure compounds isolated from four samples of Dysidea sp. sponges collected from two geographically distinct regions of the Indo-Pacific (Chuuk Atoll and Fiji) were assayed against five different enzyme assays, four of which are relevant to anticancer drug discovery and one of which (15-lipoxygenase) may detect compounds significant in modulating the development of atherosclerotic plaque. The pure compounds that inhibited various enzymes were polybrominated phenols and polybrominated phenoxyphenols. Fourteen of these phenols were isolated, six of which were new compounds. A variety of the phenols inhibited inosine monophosphate dehydrogenase (IMPDH), guanosine monophosphate synthetase, and 15-lipoxygenase. No activity was observed with protein tyrosine kinase pp60v-src or matrix metalloprotease.
Two new alkaloids, polycarpine (1) and N,N-didesmethylgrossularine-1 (4), have been isolated from extracts of the ascidian Polycarpa aurata collected in Chuuk, Federated States of Micronesia. Three degradation products of 1 were also isolated. The structures of 1, 2, and 4 were determined by X-ray crystallography. The dimeric disulfide 1 inhibited the enzyme inosine monophosphate dehydrogenase, but the inhibition could be reversed by addition of excess dithiothreitol suggesting that 1 reacts with sulfhydryl groups on the enzyme.
Guided by inhibitory activity against IMP dehydrogenase (IMPDH), a new brominated diphenylmethane derivative, isorawsonol, has been isolated from the tropical green alga Avrainvillea rawsonii. Its structure was determined by detailed spectroscopic analysis including HMQC and HMBC. The known metabolites, avrainvilleol, avrainvilleol methyl ether, 3-bromo-4,5-dihydroxylbenzyl alcohol, and rawsonol, were also isolated from this alga and two of these showed a modest ability to inhibit IMPDH. The formation of isorawsonol is envisioned as being similar to that of rawsonol involving condensation of two molecules of avrainvilleol.
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