An antimalarial screen for plants collected from Papua New Guinea identified an extract of Horsfieldia spicata as having activity. Isolation of the active constituents led to the identification of two new compounds: myristicyclins A (1) and B (2). Both compounds are procyanidin-like congeners of myristinins lacking a pendant aromatic ring. Myristicyclin A was found to inhibit the ring, trophozoite, and schizont stages of Plasmodium falciparum at similar concentrations in the mid-μM range.

Two merotriterpenoid hydroquinone sulfates designated adociasulfate-13 (1) and adociasulfate-14 (2) were purified from Cladocroce aculeata (Chalinidae) along with adociasulfate-8. All three compounds were found to inhibit microtubule-stimulated ATPase activity of kinesin at 15 µM by blocking both the binding of microtubules and the processive motion of kinesin along microtubules. These findings directly show that substitution of the 5′-sulfate in 1 for a glycolic acid moiety in 2 maintains kinesin inhibition. Nomarski imaging and bead diffusion assays in the presence of adociasulfates showed no signs of either free-floating or bead-bound adociasulfate aggregates. Single-molecule biophysical experiments also suggest that inhibition of kinesin activity does not involve adociasulfate aggregation. Furthermore, both mitotic and nonmitotic kinesins are inhibited by adociasulfates to a significantly different extent. We also report evidence that microtubule binding of nonkinesin microtubule binding domains may be affected by adociasulfates.

Two merotriterpenoid hydroquinone sulfates designated adociasulfate-13 (1) and adociasulfate-14 (2) were purified from Cladocroce aculeata (Chalinidae) along with adociasulfate-8. All three compounds were found to inhibit microtubule-stimulated ATPase activity of kinesin at 15 µM by blocking both the binding of microtubules and the processive motion of kinesin along microtubules. These findings directly show that substitution of the 5′-sulfate in 1 for a glycolic acid moiety in 2 maintains kinesin inhibition. Nomarski imaging and bead diffusion assays in the presence of adociasulfates showed no signs of either free-floating or bead-bound adociasulfate aggregates. Single-molecule biophysical experiments also suggest that inhibition of kinesin activity does not involve adociasulfate aggregation. Furthermore, both mitotic and nonmitotic kinesins are inhibited by adociasulfates to a significantly different extent. We also report evidence that microtubule binding of nonkinesin microtubule binding domains may be affected by adociasulfates.