title: New antituberculotics originated from salicylanilides with promising in vitro activity against atypical mycobacterial strains.
abstract: A new series of 30 N-protected amino acid esters were prepared as a part of ongoing search for new anti-tuberculosis active salicylanilides. The esters possess high in vitro activity against Mycobacterium tuberculosis, Mycobacterium avium, and two strains of Mycobacterium kansasii, where one is an isolate from the patient, with MIC in the range 1-32 micromol/L for all tested strains. The prepared esters can be considered as prodrugs with better bio-availability and as more efficient transport forms through the mycobacterial cell membranes due to the higher lipophilicity. The experimental and calculated lipophilicity, stability, antituberculotic activity, cytotoxicity as well as the quantitative structure-activity relationships (QSARs) explored by the Intelligent Problem Solver (IPS) in Trajan Neural Network Simulator 6.0 are presented.
authors.affiliation: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, nam. Cs. Legii 565, 532 10 Pardubice, Czech Republic. Ales.Imramovsky@upce.cz
authors.forename: Ales
authors.initials: A
authors.lastname: Imramovský
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinsová
authors.forename: Juana Monreal
authors.initials: JM
authors.lastname: Férriz
authors.forename: Rafael
authors.initials: R
authors.lastname: Dolezal
authors.forename: Josef
authors.initials: J
authors.lastname: Jampílek
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kaustová
authors.forename: Filip
authors.initials: F
authors.lastname: Kunc
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D004951:Esterification; D057927:Hydrophobic and Hydrophilic Interactions; D009170:Nontuberculous Mycobacteria / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D012458:Salicylanilides / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D000995:Antitubercular Agents; D012458:Salicylanilides