title: Three new fusidic acid derivatives and their antibacterial activity.
abstract: Two steroid acids, cephalosporin P1 and isocephalosporin P1, 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 P1, 3-keto-cephalosporin P1 and 6-deacetyl-3-keto-cephalosporin P1. The final pH of the bacterial culture was 9.0. Incubation of 3-keto-isocephalosporin P1 or 3-keto-cephalosporin P1 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 P1. These fusidic acid derivatives were tested for the antibacterial activity against the Gram-positive pathogen Staphylococcus aureus. 3-Keto-cephalosporin P1 showed the highest activity among the five compounds, with a minimal inhibition concentration (MIC) of 4 μg/mL, which is more potent than the substrate cephalosporin P1. Both cephalosporin P1 and 3-keto-cephalosporin P1 were active against methicillin-resistant S. aureus, with the same MIC of 8 μg/mL.
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322, United States.
authors.forename: Cheng-Wei Tom
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States. Electronic address: jixun.zhan@usu.edu.
authors.forename: Jixun
authors.initials: J
authors.lastname: Zhan
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005672:Fusidic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005672:Fusidic Acid
keywords: Antibacterial; Biotransformation; Dehydrogenation; Fusidic acid; Hapsidospora irregularis; Microbacterium oxydans
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