Nannozinones and sorazinones, unprecedented pyrazinones from myxobacteria.

Abstract

Nannozinones A (1) and B (2) were discovered as metabolites of the recently isolated Nannocystis pusilla strain MNa10913 belonging to the poorly studied myxobacterial family Nannocystaceae. In contrast, the structurally related sorazinones A (5) and B (6) were isolated from Sorangium cellulosum strain Soce895, which was known as the producer of the antibiotic thuggacin A. The extract also contained methyl indole-3-carboxylate (4). HRESIMS and (1)H, (13)C, and (15)N NMR spectroscopy revealed the structures of nannozinones A (1) and B (2) as unusual dihydropyrrolo- and pyrrolopyrazinone derivatives, while sorazinone A (5) was characterized as an aromatic diketopiperazine and sorazinone B (6) as a dibenzyl 2(1H)-pyrazinone derivative. While the dihydropyrrolo derivative nannozinone A (1) showed weak antibacterial and antifungal activity, nannozinone B (2) inhibited the growth of cell cultures with IC50 values between 2.44 and 16.9 μM. The nannochelin A iron complex (3), which was isolated besides 1 and 2, was even more active, with IC50 values between 0.05 and 1.95 μM. On the other hand, the indole 4 and sorazinones 5 and 6 did not show any significant cytotoxicity and only weak activity against the Gram-positive Nocardia sp.