title: Novel camphane-based anti-tuberculosis agents with nanomolar activity.
abstract: A series of new amidoalcohols and amidodiols were designed on the base of the camphor scaffold and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv and MDR strain 43. Some of the new compounds show 25 times higher activity than the classical anti-TB drug ethambutol. Small structural changes in the side chain shift the activity from micromolar to nanomolar inhibitory concentrations. Quantitative structure-activity relationship (QSAR) model is derived to guide the further lead optimization. Two hydrogen bond donors and up to three rings in the molecules are optimal for nanomolar activity. The camphane-based amides present novel promising scaffolds for antimycobacterial agents.
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria. Electronic address: gstavrakov@pharmfac.net.
authors.forename: Georgi
authors.initials: G
authors.lastname: Stavrakov
authors.forename: Violeta
authors.initials: V
authors.lastname: Valcheva
authors.forename: Irena
authors.initials: I
authors.lastname: Philipova
authors.forename: Irini
authors.initials: I
authors.lastname: Doytchinova
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*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001892:Camphanes; C067796:camphane
keywords: Antimycobacterial activity; Camphane; M. tuberculosis H37Rv; MDR; QSAR