Napyradiomycin B3

Structures of novel antibiotics, napyradiomycins A, B1, B2, B3, C1 and C2 were determined. By X-ray crystallography, napyradiomycin B2 was determined to be (3R,10aR)-3-chloro-10a-[[(1R,3S)-3-chloro-2, 2-dimethyl-6-methylenecyclohexyl]methyl]-3,10a-dihydro-6,8-dihydro xy-2, 2-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione. The structures of other napyradiomycins were elucidated by NMR studies. Napyradiomycins C1 and C2 have unique structures which contain 14-membered ring cyclized by carbon-carbon bond.

Novel antibacterial antibiotics napyradiomycins A, B1, B2, B3, C1 and C2 have been isolated from the culture broth of Chainia rubra MG802-AF1. In this paper, taxonomy of the producer, and production, isolation, physico-chemical properties and biological activities of napyradiomycins are reported. They contain the naphtopyran chromophore and halogens, and inhibit the growth of Gram-positive bacteria including drug-resistant strains.

Three new napyradiomycins (1-3) were isolated from the culture broth of a marine-derived actinomycete strain SCSIO 10428, together with six known related analogues napyradiomycin A1 (4), 18-oxonapyradiomycin A1 (5), napyradiomycin B1 (6), napyradiomycin B3 (7), naphthomevalin (8), and napyradiomycin SR (9). The strain SCSIO 10428 was identified as a Streptomyces species by the sequence analysis of its 16S rRNA gene. The structures of new compounds 1-3, designated 4-dehydro-4a-dechlorona pyradiomycin A1 (1), 3-dechloro-3-bromonapyradiomycin A1 (2), and 3-chloro-6, 8-dihydroxy-8-α-lapachone (3), respectively, were elucidated by comparing their 1D and 2D NMR spectroscopic data with known congeners. None of the napyradiomycins 1-9 showed antioxidative activities. Napyradiomycins 1-8 displayed antibacterial activities against three Gram-positive bacteria Staphylococcus and Bacillus strains with MIC values ranging from 0.25 to 32 μg mL⁻¹, with the exception that compound 3 had a MIC value of above 128 μg mL⁻¹ against Staphylococcus aureus ATCC 29213. Napyradiomycins 2, 4, 6, and 7 exhibited moderate cytotoxicities against four human cancer cell lines SF-268, MCF-7, NCI-H460, and HepG-2 with IC₅₀ values below 20 μM, while the IC₅₀ values for other five napyradiomycins 1, 3, 5, 8 and 9 were above 20 μM.