title: Synthesis, characterization and in vitro extracellular and intracellular activity against Mycobacterium tuberculosis infection of new second-line antitubercular drug-palladium complexes.
abstract: OBJECTIVE
  The aim of this work was to characterize novel palladium (Pd) complexes with second-line antitubercular drugs, namely capreomycin (C), kanamycin (K) and ofloxacin (Ofx), and to address the in vitro extracellular and intracellular activity against Mycobacterium tuberculosis infection.
  
  
  METHODS
  Synthesis reaction kinetics and complex properties were assessed. Kf was calculated from the transition state quasi-equilibrium approximation and Arrhenius plot. The complexes were characterized for qualitative solubility, stoichiometry, powder size and morphology, element analysis, and thermal behaviour. Structural analyses were performed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Activity was evaluated against H37Ra M. tuberculosis strain and in infected THP-1 cells, and compared with that of the parent drugs.
  
  
  RESULTS
  The complexes showed log Kf of 6 for CPd and OfxPd, and 10 for KPd indicating good stability. Stoichiometry of 1:1, 2: 3 and 1:3 resulted for OfxPd, KPd, and CPd. OfxPd structure matched that in literature, while K and C had more complex structures with possible multiple coexisting species. The complexes had extracellular activity comparable with drugs and an improved efficacy against intracellular infection of M. tuberculosis.
  
  
  CONCLUSIONS
  The novel anti-tuberculosis (TB) complexes had promising properties, and extracellular and intracellular activity, which makes them potential tools for intracellular targeting of pulmonary TB.
authors.affiliation: Department of Chemistry and Technology of Drugs, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Giovagnoli
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Marenzoni
authors.forename: Morena
authors.initials: M
authors.lastname: Nocchetti
authors.forename: Claudio
authors.initials: C
authors.lastname: Santi
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Aurelie
authors.initials: A
authors.lastname: Schoubben
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ricci
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002207:Capreomycin / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry* / Q000494:pharmacology*; D010316:Particle Size; D012995:Solubility; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D002207:Capreomycin; D007612:Kanamycin; D010165:Palladium; D015242:Ofloxacin
keywords: capreomycin; drug-palladium complexes; intracellular antitubercular activity; kanamycin; ofloxacin