title: Antibacterial activity of salicylanilide 4-(trifluoromethyl)-benzoates.
abstract: The development of novel antimicrobial agents represents a timely research topic. Eighteen salicylanilide 4-(trifluoromethyl)benzoates were evaluated against Mycobacterium tuberculosis, M. avium and M. kansasii, eight bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and for the inhibition of mycobacterial isocitrate lyase. Some compounds were further screened against drug-resistant M. tuberculosis and for their cytotoxicity. Minimum inhibitory concentrations (MICs) for all mycobacterial strains were within 0.5-32 μmol/L, with 4-chloro-2-[4-(trifluoromethyl)phenylcarbamoyl]phenyl 4-(trifluoromethyl)benzoate superiority. Gram-positive bacteria including MRSA were inhibited with MICs ³ 0.49 μmol/L, while Gram-negative ones were much less susceptible. Salicylanilide 4-(trifluoromethyl)benzoates showed significant antibacterial properties, for many strains being comparable to standard drugs (isoniazid, benzylpenicillin) with no cross-resistance. All esters showed mild inhibition of mycobacterial isocitrate lyase and four compounds were comparable to 3-nitropropionic acid without a direct correlation between in vitro MICs and enzyme inhibition.
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. martin.kratky@faf.cuni.cz
authors.forename: Martin
authors.initials: M
authors.lastname: Krátký
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinšová
authors.forename: Eva
authors.initials: E
authors.lastname: Novotná
authors.forename: Jana
authors.initials: J
authors.lastname: Mandíková
authors.forename: František
authors.initials: F
authors.lastname: Trejtnar
authors.forename: Jiřina
authors.initials: J
authors.lastname: Stolaková
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects; D019909:Mycobacterium kansasii / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009574:Nitro Compounds / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D012458:Salicylanilides / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001565:Benzoates; D009574:Nitro Compounds; D011422:Propionates; D012458:Salicylanilides; D007522:Isocitrate Lyase; C034596:salicylanilide; C015392:3-nitropropionic acid