Title

Antimalarial Properties of Simplified Kalihinol Analogues

ACS Citation

Daub, M. E.; Prudhomme, J.; Ben Mamoun, C.; Le Roch, K. G.; Vanderwal, C. D.; Antimalarial Properties of Simplified Kalihinol Analogues. ACS Med. Chem. Lett. 2017, 8, 355–360.

Abstract

Several kalihinol natural products, members of the broader isocyanoterpene family of antimalarial agents, are potent inhibitors of Plasmodium falciparum, the agent of the most severe form of human malaria. Our previous total synthesis of kalihinol B provided a blueprint to generate many analogues within this family, some as complex as the natural product and some much simplified and easier to access. Each analogue was tested for blood-stage antimalarial activity using both drug-sensitive and -resistant P. falciparum strains. Many considerably simpler analogues of the kalihinols retained potent activity, as did a compound with a different decalin scaffold made in only three steps from sclareolide. Finally, one representative compound showed reasonable stability toward microsomal metabolism, suggesting that the isonitrile functional group that is critical for activity is not an inherent liability in these compounds.

Source Name

ACS Medicinal Chemistry Letters

Publication Date

2-16-2017

Volume

8

Issue

3

Page(s)

355-360

Document Type

Article

Citation Type

Article

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