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