Synthesis, characterization and in vitro extra- and intracellular activity against Mycobacterium tuberculosis infection of new second-line antitubercular drug-palladium complexes.

Objectives. 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, extra- 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, thermal behavior. Structural analyses were performed by FTIR and NMR. Activity was evaluated against H37Ra M. tuberculosis strain and in infected THP-1 cells and compared to that of the parent drugs. Key findings. The complexes showed log Kf of 6 for CPd and OfxPd and 10 for KPd indicating good stability. Stoichiometry of 1:1, 2:3, 1:3 resulted for OfxPd, KPd, 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 to drugs and an improved efficacy against intracellular infection of Mycobacterium tuberculosis. Conclusions. The novel anti-TB complexes had promising properties and extra- and intracellular activity, which makes them potential tools for intracellular targeting of pulmonary TB.