Synthesis, characterization, and biological evaluation of hybrid copper(ii) complexes containing azole drugs and planar ligands against neglected diseases

Motivated by the urgent need to find new agents for the treatment of leishmaniasis and fungal infections, six copper(II) coordination complexes containing well-known azole drugs with antifungal and antiparasitic properties, i.e., ketoconazole (KTZ), clotrimazole (CTZ), and fluconazole (FLZ), were synthesized. By reacting copper(II) complexes containing a bidentate planar ligand, either 1,10-phenanthroline (phen) or 1,10phenanthroline-5,6-dione (dione), with azole drugs under mild conditions, we synthesized the set of compounds investigated in this work, i.e., [Cu(phen)(CTZ)(2)(NO3)](NO3)center dot 4H(2)O (1), [Cu(phen)(KTZ)(2)(NO3)](NO3)center dot 3H(2)O center dot C2H10O (2), [Cu(phen)(FLZ)(NO3)](2)(NO3)(2)center dot 5H(2)O (3), [Cu(dione)(CTZ)(2)(NO3)](NO3)center dot 5H(2)O (4), [Cu(dione)(KTZ)(2)(NO3)](NO3)center dot 5H(2)O (5), and [Cu(phen)(FLZ)(NO3)](2)center dot(NO3)(2)center dot 5H(2)O (6). Chemical composition and structural features of the copper(II) complexes were characterized in depth using multiple analytical and spectroscopic techniques, i.e., conductivity measurements, elemental analysis, infrared (FT-IR), UV-Visible (UV-Vis), and electron paramagnetic resonance (EPR) spectroscopies. Furthermore, the stability of these complexes was validated through spectrophotometric measurements of aqueous solutions. Antileishmanial and antifungal properties were analyzed in vitro. Our results pointed out a remarkable anti-leishmanial activity for some of the investigated systems and a promising anti-Sporothrix activity for the complex [Cu(phen)(KTZ)(2)(NO3)]NO3.