title: Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity.
abstract: Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32 μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2 μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98 μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Georgios
authors.initials: G
authors.lastname: Paraskevopoulos
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Krátký
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Mandíková
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Trejtnar
authors.affiliation: Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic.
authors.forename: Jiřina
authors.initials: J
authors.lastname: Stolaříková
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Pávek
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Gurdyal
authors.initials: G
authors.lastname: Besra
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: jarmila.vinsova@faf.cuni.cz.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinšová
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016983:Enterococcus / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012458:Salicylanilides / Q000737:chemistry / Q000494:pharmacology; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D012458:Salicylanilides; D012459:Salicylates
keywords: Cytotoxicity; In silico ADMET prediction; In vitro antimicrobial activity; In vitro antimycobacterial activity; Nitro group; Salicylanilides