title: Syntheses and evaluation of substituted aromatic hydroxamates and hydroxamic acids that target Mycobacterium tuberculosis.
abstract: Tuberculosis (TB) continues to remain one of the most threatening diseases in the world. With the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains, the need to develop new therapies is dire. The syntheses of a focused library of hydroxamates and hydroxamic acids is described, as well as anti-TB activity in the microplate alamar blue assay (MABA). A number of compounds exhibited good activity against Mtb, with notable compounds exhibiting MIC values in the range of 20-0.71 μM. This work suggests that both hydroxamates and their free acids may be incorporated into more complex scaffolds and serve as potential leads for the development of anti-TB agents.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Majewski
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, MIC 964, Rm. 412, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Miller
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, MIC 964, Rm. 412, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: mmiller1@nd.edu.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Miller
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D006841:Hydrocarbons, Aromatic; D006877:Hydroxamic Acids
keywords: Hydroxamate; Hydroxamic acid; Tuberculosis