MDN-0185, an Antiplasmodial Polycyclic Xanthone Isolated from <i>Micromonospora</i> sp. CA-256353

A potent antiplasmodial polycyclic xanthone, MDN-0185 (<b>1</b>), was isolated from an unidentified species of the genus <i>Micromonospora</i>. The planar structure of <b>1</b> was established as a seven-ring polycyclic xanthone with partial structures very similar to two known natural products, namely, xantholipin and Sch 54445. Using ROESY correlations, the relative stereochemistry of the two independent stereoclusters of compound <b>1</b> could be determined. Mosher analysis and comparison of the specific rotation of compound <b>1</b> with that of xantholipin allowed the determination of its absolute configuration. Compound <b>1</b> exhibited an IC₅₀ of 9 nM against <i>Plasmodium falciparum</i> 3D7 parasites

MDN-0104, an Antiplasmodial Betaine Lipid from <i>Heterospora chenopodii</i>

Bioassay-guided fractionation of the crude fermentation extract of <i>Heterospora chenopodii</i> led to the isolation of a novel monoacylglyceryltrimethylhomoserine (<b>1</b>). The structure of this new betaine lipid was elucidated by detailed spectroscopic analysis using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. Compound <b>1</b> displayed moderate <i>in vitro</i> antimalarial activity against <i>Plasmodium falciparum</i>, with an IC₅₀ value of 7 μM. This betaine lipid is the first monoacylglyceryl­trimethyl­homoserine ever reported in the Fungi, and its acyl moiety also represents a novel natural 3-keto fatty acid. The new compound was isolated during a drug discovery program aimed at the identification of new antimalarial leads from a natural product library of microbial extracts. Interestingly, the related fungus <i>Heterospora dimorphospora</i> was also found to produce compound <b>1</b>, suggesting that species of this genus may be a promising source of monoacylglyceryltrimethylhomoserines

Lasionectrin, a Naphthopyrone from a <i>Lasionectria</i> sp.

A new naphthopyrone derivative, lasionectrin (<b>1</b>), was isolated from fermentations of an <i>Acremonium</i>-like fungus provisionally identified as a <i>Lasionectria</i> sp. (Ascomycota, Hypocreales) and isolated from forest leaf litter from Equatorial Guinea. Its structure was determined by a combination of spectroscopic techniques, including UV, (+)-HRESIMS, and 1D and 2D NMR spectroscopy, and comparison with published data for related fungal metabolites. Compound <b>1</b> inhibited the growth of <i>Plasmodium falciparum</i> with an IC₅₀ value of 11 μM