Three new fusidic acid derivatives and their antibacterial activity

Two steroid acids, cephalosporin P-1 and isocephalosporin P-1, were isolated from Hapsidospora irregularis FERM BP-2511. These compounds are structurally related to fusidic acid. Their NMR data were completely assigned on the basis of the 2D NMR spectra. Incubation of these two compounds with Microbacterium oxydans CGMCC 1788 in Luria-Bertani broth yielded the same set of three new 3-dehydrogenated products, 3-keto-isocephalosporin P-1, 3-keto-cephalosporin P-1 and 6-deacetyl-3-keto-cephalosporin P-1. The final pH of the bacterial culture was 9.0. Incubation of 3-keto-isocephalosporin P-1 or 3-keto-cephalosporin P-1 in Tris-HCl buffer ( pH 9.0) revealed that these two compounds can convert to each other by shifting the acetyl group between C-6 and C-7. The acetyl group at C-6 or C-7 can also be removed by hydrolysis to yield the minor product 6-deacetyl-3-keto-cephalosporin P-1. These fusidic acid derivatives were tested for the antibacterial activity against the Gram-positive pathogen Staphylococcus aureus. 3-Keto-cephalosporin P-1 showed the highest activity among the five compounds, with a minimal inhibition concentration ( MIC) of 4 mu g/mL, which is more potent than the substrate cephalosporin P-1. Both cephalosporin P-1 and 3-keto-cephalosporin P-1 were active against methicillin-resistant S. aureus, with the same MIC of 8 mu g/mL. (C) 2015 Elsevier Ltd. All rights reserved.