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

• Published in: New journal of chemistry 2024-02, Vol.48 (6), p.2515-2526
• Main Authors: de Azevedo-França, José Aleixo, Feliciano dos Santos Ramos, Victor, Messori, Luigi, Santanni, Fabio, Sorace, Lorenzo, Pereira Borba-Santos, Luana, Rozental, Sonia, Cola Fernandes Rodrigues, Juliany, Navarro, Maribel
• Format: Article
• Language: English
• Subjects: Aqueous solutions; Chemical analysis; Chemical composition; Coordination compounds; Copper; Drugs; Electron paramagnetic resonance; Fungicides; Infrared analysis; Ligands; Spectrophotometry; Synthesis; Tropical diseases
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d3nj04608g

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 1,10-phenanthroline-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 (NO 3 )](NO 3 )·4H 2 O ( 1 ), [Cu(phen)(KTZ) 2 (NO 3 )](NO 3 )·3H 2 O·C 2 H 10 O ( 2 ), [Cu(phen)(FLZ)(NO 3 )] 2 (NO 3 ) 2 ·5H 2 O ( 3 ), [Cu(dione)(CTZ) 2 (NO 3 )](NO 3 )·5H 2 O ( 4 ), [Cu(dione)(KTZ) 2 (NO 3 )](NO 3 )·5H 2 O ( 5 ), and [Cu(phen)(FLZ)(NO 3 )] 2 ·(NO 3 ) 2 ·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 (NO 3 )]NO 3 . Motivated by the urgent need to find new medications for the treatment of neglected diseases, six copper( ii ) hybrid containing azole drugs and planar ligand were developed and tested against leishmania parasites and fungi.