Quinolactacins A (1), B (2) and C (3), novel quinolone antibiotics have been found from the cultured broth of a fungal strain isolated from the larvae of the mulberry pyralid (Margaronia pyloalis Welker). The fungal strain, EPF-6 was identified as Penicillium sp. from its morphological characteristics. Quinolactacins were obtained from the culture medium by solvent extraction and chromatographic purification. Compound 1 showed inhibitory activity against tumor necrosis factor (TNF) production induced by murine peritoneal macrophages and macrophage-like J774.1 cells stimulated with lipopolysaccharide (LPS).
Three novel quinolone compounds, quinolactacins A (1), B (2) and C (3), Have been found from the fermentation broth of Penidllium sp. EPF-6, a fungus isolated from the larvae of mulberry pyralid (Margaronia pyloalis Welker). The molecular formulas of 1, 2 and 3 were determined to be C16H18N2O2, C15H16N2O2 and C16H18N2O3, respectively by FAB-MS and NMR spectral analyses. The structures of these compounds have a novel quinolone skeleton with a γ-lactam ring consisting of C12H8N2O2 as the common chromophore.
The cell-free extract of an albonoursin-producing strain Streptomyces albulus KO-23 catalyzes the conversion of cyclo(L-Leu-L-Phe) (1) to albonoursin (2). At the early stage of this conversion, two compounds were newly formed prior to albonoursin synthesis in the reaction mixture. These compounds were isolated and identified as (Z)-3-benzylidene-6-isobutyl-2, 5-piperazinedione (4) and (Z)-3-benzyl-6-isobutylidene-2, 5-piperazineclione (3). The cell-free extract also catalyzed the conversion of compound 3 or 4 to albonoursin. From these results, albonoursin was found to be biosynthesized via these compounds from cyclo(L-Leu-L-Phe). These didehydro diketopiperazines exhibited no inhibitory activity toward the first cleavage of sea urchin embryo in contrast to the higher cytotoxicity for albonoursin, indicating that dehydrogenation at α, β-positions of both amino acid residues in diketopiperazines is required for cytotoxicity.
Blasticidin A, an antibiotic, showed strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. Its structure was characterized by NMR and chemical degradation experiments as 1, which is a tetramic acid derivative with a highly oxygenated long alkyl chain similar to aflastatin A (2). Absolute configurations of the eight chiral centers at C-4, 6, 31, 32, 33, 34, 35 and 37 of 1 were chemically determined. Blasticidin A almost completely inhibited aflatoxin production at 0.5 μM.
The discovery of RWJ-54428 (MC-02, 479), a new cephalosporin displaying promising activity against sensitive and resistant Gram-positive bacteria, is described. Progressive structural modification from the previously reported 3-phenylthiocephem MC-02, 331 afforded an overall increase in potency against MRSA while retaining other key properties such as acceptable solubility and serum binding. Evaluation of the in vitro potency and in vivo efficacy of a series of closely related compounds resulted in selection of RWJ-54428 (MC-02, 479) for further studies.
SB-219383 is a naturally occurring antibiotic, which acts by inhibition of tyrosyl tRNA synthetase. Semi-synthetic derivatives of SB-219383 were prepared with the objective of elucidating the key features required for inhibition of tyrosyl tRNA synthetase in order to improve the antibacterial activity. Some ester and amide derivatives as well as monocyclic analogues exhibited sub-nanomolar inhibitory activity against tyrosyl tRNA synthetase.