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

Isolation and Structural Elucidation of Cyclic Tetrapeptides from <i>Onychocola sclerotica</i>

Three new cyclic tetrapeptides (<b>1</b>–<b>3</b>) have been isolated from the crude fermentation extract of <i>Onychocola sclerotica</i>. The planar structures of <b>1</b>–<b>3</b> were elucidated by detailed spectroscopic analyses using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. The absolute configuration of the amino acid residues in each cyclotetrapeptide was established by Marfey’s method. Compounds <b>1</b>–<b>3</b> displayed activity as cardiac calcium channel blockers (Cav1.2) but did not inhibit the hERG potassium channel and were not cytotoxic. These peptides are the first secondary metabolites ever reported from fungi of the order Arachnomycetales