title: Anti-mycobacterial activity of 1,3-diaryltriazenes.
abstract: The rapid generation and spread of the drug resistant tuberculosis has led to an ongoing demand for novel compounds for therapeutic use. Identification and study of compounds with the ability to inhibit Mycobacterium tuberculosis is of paramount importance. For this reason, a library of substituted 1,3-diaryltriazenes based on the acting component of the anti-trypanosomal drug, diminazene aceturate was created and evaluated for its potential as anti-tubercular agent. Several compounds were identified with sub-micro molar inhibitory concentrations against M. tuberculosis and other clinically relevant mycobacterial species such as Mycobacterium bovis, Mycobacterium avium and Mycobacterium ulcerans. Although the library of the compounds showed a considerable acute cytotoxicity, a genotoxicity could not be observed. Finally, the triazene 14 was selected with the best biological properties (IC50 = 3.26 μM, NI50 = 24.22 μM, SI = 7.44). The compound 14 showed the ability to inhibit the growth of intracellular replicating and multi-drug resistant M. tuberculosis. The results suggest the molecule to be an interesting scaffold for further study and optimization.
authors.affiliation: Scientific Service Immunology, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium.
authors.forename: Davie
authors.initials: D
authors.lastname: Cappoen
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
authors.forename: Jure
authors.initials: J
authors.lastname: Vajs
authors.affiliation: Scientific Service Immunology, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Uythethofken
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Virag
authors.affiliation: Program Tuberculosis and Mycobacteria, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mathys
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
authors.forename: Marijan
authors.initials: M
authors.lastname: Kočevar
authors.affiliation: Program Toxicology, O.D. Public Health and Surveillance, Scientific Institute of Public Health (Site Elsene), J. Wytsmanstraat 14, B-1050 Brussels, Belgium; Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Verschaeve
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
authors.forename: Martin
authors.initials: M
authors.lastname: Gazvoda
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
authors.forename: Slovenko
authors.initials: S
authors.lastname: Polanc
authors.affiliation: Scientific Service Immunology, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium. Electronic address: kris.huygen@wiv-isp.be.
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia. Electronic address: janez.kosmrlj@fkkt.uni-lj.si.
authors.forename: Janez
authors.initials: J
authors.lastname: Košmrlj
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009162:Mycobacterium avium / Q000187:drug effects* / Q000254:growth & development; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000254:growth & development; D019911:Mycobacterium ulcerans / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D014226:Triazenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D014226:Triazenes
keywords: 1,3-Diaryltriazene; Acute toxicity; Antibiotic lead; Genotoxicity; SAR; Tuberculosis