Nannozinones and sorazinones, unprecedented pyrazinones from myxobacteria.
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.
Department of Microbial Drugs, §Research Group Microbial Communication, Helmholtz Centre for Infection Research , Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Rolf
R
Jansen
Sakshi
S
Sood
Kathrin I
KI
Mohr
Brigitte
B
Kunze
Herbert
H
Irschik
Marc
M
Stadler
Rolf
R
Müller
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry*; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D012988:Soil Microbiology; D013030:Spain
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007211:Indoles; D011719:Pyrazines; D011758:Pyrroles; C000599244:nannozinone A; C000599245:nannozinone B; C000599246:sorazinone A; C000599247:sorazinone B