title: Synthesis and antimycobacterial activity of novel camphane-based agents.
abstract: A series of six new amidoalcohols was designed and synthesized on the base of the camphor scaffold. Natural amino acids were transformed into their α-hydroxy analogues with retention of configuration, and attached to isobornylamine. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Some of the new compounds show 25 times higher activity than the classical anti-TB drug ethambutol. The activity shifts from micromolar to nanomolar inhibitory concentrations depending on the α-hydroxy acid moiety. Two of the most potent compounds exert low level of cytotoxic activity. These camphane-based amido-alcohols present promising potential lead compounds for further elaboration of antimycobacterial agents.
authors: Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria. Electronic address: gstavrakov@pharmfac.net.
authors: Georgi
authors: G
authors: Stavrakov
authors: Institute of Organic Chemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria.
authors: Irena
authors: I
authors: Philipova
authors: Institute of Microbiology, Bulgarian Academy of Sciences, Akad. Bonchev 26, Sofia 1113, Bulgaria.
authors: Violeta
authors: V
authors: Valcheva
authors: Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria.
authors: Georgi
authors: G
authors: Momekov
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001892:Camphanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001892:Camphanes; C067796:camphane
keywords: Antimycobacterial activity; Camphane; Isobornylamine; M. tuberculosis H37Rv; α-Hydroxy acids