Axisonitrile antimalarial

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. 

In principle, the sharing of the same mechanism of action of chloroquine could be a weak point for isonitrile antimalarials indeed, in this case, cross-resistance phenomena could be stimulated. However, the remarkable selective activity of axisonitrile-3 on chloroquine-resistant strains (see before) encourages further studies. 

Isonitriles are stable, often naturally occurring, compounds that contain a divalent carbon. An example is axisonitrile-3, which can be isolated from a species of sponge and possesses antimalarial activity. Write a resonance form for axisonitrile-3 that satisfies the octet rule. Don t forget to include formal charges. 

Tamura, K Nakazaki, A., and Kobayashi, S. (2009) StereocontroUed total synthesis of antimalarial (-F)-axisonitrile-3. Synlett. 2449-2452. 

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