Acanthella klethra

During our studies of the kalihinols (Sect. 4.2.2), isothiocyanate 28 was one of several isocyano-related compounds isolated from Acanthella klethra from Australia. Its structure was also published independently from a Ciocalypta sp. in Hawaii [37] and reported as a poster at the 1988 Gordon Research Confer-... 

Angerhofer CK, Pezzuto JM, Koenig GM, Wright AD, Sticher O. (1992) Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra. J Nat Prod 55 1787-1789. 

Three new antiparasitic sesquiterpene isothiocyanates, 4-isothiocyanato-9-amorphene (264), 10-isothiocyanato-4,6-amorphadiene (265) and 10-isothiocyanato-5-amorphen-4-ol (266) were isolated from a Fijian specimen of Axinyssa fenestratus. The compounds were identified by spectral data interpretation [268]. Two isomeric isothiocyanates (267-268) were isolated from Acanthella klethra from the Great Barrier Reef and their structures were determined by X-ray crystallography and spectral data examination [269]. 

Almost twenty years later, axisonitrile-3 (11) was re-isolated from the sponge Acanthella klethra Pulitzer-Finali and found to possess a potent antimalarial activity both on chloroquine-sensitive (D6, 142 ng/mL) and chloroquine-resistant (W2, 17 ng/mL) P. falciparum strains, with an activity ten times higher on the chloroquine-resistant one [32]. The closely related axisothiocyanate-3 (12) was practically inactive, giving the first suggestion that the antiplasmodial activity should not (or, at least, not only) be ascribed to structural features of the carbon backbone but should be strictly dependent from the presence of the isonitrile functional group. Interestingly, axisonitrile-3 was found to be practically not cytotoxic toward KB cells. 

As early as 1992, with the discovery of axisonitrile-3 in the species Acanthella klethra (see below), it became apparent that the isonitrile group is involved in the process of heme... 

Fusetani, N., Yasumoro, K., Kawai, H., Natori, T, Brinen, L., and Clardy, J. (1990b) Kalihinene and isokalihinol B, cytotoxic diterpene isoiutriles from the marine sponge Acanthella klethra. Tetrahedron Lett., 31, 3599-3602. 

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