title: The abyssomicin C family as in vitro inhibitors of Mycobacterium tuberculosis.
abstract: The antimycobacterial efficacy of the abyssomicin C family of natural products, in addition to a key synthetic intermediate, has been investigated given their reported inhibition of Bacillus subtilis p-aminobenzoate biosynthesis. The naturally occurring (-)-abyssomicin C and its atropisomer were found to exhibit low micromolar growth inhibition against the relatively fast-growing and non-virulent Mycobacterium smegmatis and the vaccine strain Mycobacterium bovis BCG, while their antipodes were slightly less active. (-)-abyssomicin C and its atropisomer were particularly efficacious against Mycobacterium tuberculosis H37Rv, exhibiting MIC values of 3.6 and 7.2 μM, respectively. More specifically, (-)-abyssomicin C was bactericidal. This complex natural product and its analogs, thus, hold promise as chemical tools in the study of M. tuberculosis metabolism.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-8128, USA. joelf@tamu.edu
authors.forename: Joel S
authors.initials: JS
authors.lastname: Freundlich
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Lalgondar
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Wei
authors.forename: Stephanie
authors.initials: S
authors.lastname: Swanson
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Sorensen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
authors.forename: James C
authors.initials: JC
authors.lastname: Sacchettini
mesh_terms: D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000995:Antitubercular Agents / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C509797:abyssomicin C; D010129:4-Aminobenzoic Acid