title: Potential of Casiopeínas® Copper Complexes and Antituberculosis Drug Combination against Mycobacterium tuberculosis.
abstract: New compounds with antituberculosis activity and their combination with classic drugs have been evaluated to determine possible interactions and antagonism. The aim of this study was to evaluate the in vitro activity of Casiopeínas® copper-based compounds (CasIIIia, CasIIIEa, and CasIIgly) alone and combined with isoniazid (INH), rifampicin, or ethambutol (EMB) against resistant and susceptible Mycobacterium tuberculosis. Seventeen clinical M. tuberculosis isolates (5 multi-drug resistant and 2 resistant to INH and/or EMB) were subjected to determination of the minimal inhibitory concentration (MIC) by the resazurin microtiter assay and combination assessment by the resazurin drug combination microtiter assay. The Casiopeínas® alone showed a remarkable effect against resistant isolates with MIC values from 0.78 to 12.50 μg/ml. Furthermore, a synergistic effect mainly with EMB is shown for both resistant and susceptible clinical isolates. Casiopeínas® are promising candidates for future investigation into the development of antituberculosis drugs, being one of the first examples of essential metal-based drugs used in this field.
authors.forename: A R
authors.initials: AR
authors.lastname: Barbosa
authors.forename: K R
authors.initials: KR
authors.lastname: Caleffi-Ferracioli
authors.forename: C Q F
authors.initials: CQ
authors.lastname: Leite
authors.forename: J C
authors.initials: JC
authors.lastname: García-Ramos
authors.forename: Y
authors.initials: Y
authors.lastname: Toledano-Magaña
authors.forename: L
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.forename: V L D
authors.initials: VL
authors.lastname: Siqueira
authors.forename: F R
authors.initials: FR
authors.lastname: Pavan
authors.forename: R F
authors.initials: RF
authors.lastname: Cardoso
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D004977:Ethambutol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D056831:Coordination Complexes; D003300:Copper; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin