Pyrronazols, Metabolites from the Myxobacteria <i>Nannocystis pusilla</i> and <i>N. exedens</i>, Are Unusual Chlorinated Pyrone-Oxazole-Pyrroles

The chlorinated pyrrole-oxazole-pyrones pyrronazol A (<b>1</b>), pyrronazol A2 (<b>2</b>), and pyrronazol B (<b>3</b>) were isolated from <i>Nannocystis pusilla</i> strain Ari7, and two chlorinated pyrrole-oxazole isomers, pyrronazols C1 (<b>4</b>) and C2 (<b>5</b>), were isolated from <i>N. pusilla</i> strain Na a174. HRESIMS, NMR, and X-ray crystallographic analysis was used in the structure elucidation including the absolute configuration of pyrronazol A (<b>1</b>). In addition to pyrronazols, 1,6-phenazine-diol (<b>6</b>) and its glycosyl derivative, 1-hydroxyphenazin-6-yl-α-d-arabinofuranoside (<b>7</b>), were isolated and identified from the culture broth of <i>N. pusilla</i> strain Ari7. When tested for biological activity against bacteria, fungi, and yeasts, <b>1</b> showed weak antifungal activity against <i>Mucor hiemalis</i> (MIC 33.3 μg/mL) but no antibacterial activity, while <b>6</b> showed weak antibacterial and antifungal activity (MIC 33.3 μg/mL) against some of the strains tested. In cell culture experiments <b>1</b> showed no significant cytotoxicity, while <b>6</b> was active against several cell lines, especially the human ovarian carcinoma cells SK-OV-3 (LD₅₀ 2.59 μM)