Pharmacological properties of the [Cu(sulfadiazine)(2,2′-bipyridine)Cl] coordination compound

CADAVID VARGAS J.F.; VILLA-PÉREZ, C.; SORIA D.B.; MEDINA, JUAN J. MARTÍNEZ; DI VIRGILIO A.L.

Congreso; Reunión anual de Sociedades de Biociencias (SAIC, SAB, AAFE, AACYTAL); 2023

Objectives. The main purpose of this study was to synthesize a ternary Cu(II) complex of sulfadiazine (SDZ) - an antibacterial and antimalarial drug - which includes the 2,2′-bipyridine (bipy) as co-ligand, named Cu(SDZ)bipyCl. The assessment of this complex´s toxicological along with the antimicrobial and antitumor features is reported here.Methods. The safety profile was assessed in terms of mutagenicity by the Ames Test using two Salmonella strains and acute toxicity by the Artemia salina assay. The antimicrobial activity was studied against bacteria and fungi by the agar dilution method. The minimum inhibitory concentration (MIC) was determined against 10 ATCC strains and 10 clinical isolates strains. Moreover, the cytotoxic activity was determined using the MTT method in two tumoral cell lines. Results. Our findings showed that this complex induces neither mutagenicity (frameshift mutations on S. typhimurium TA98 or base-pair substitution mutations on S. typhimurium TA100) nor acute toxicity on A. salina nauplii (until 600 µg mL-1). SDZ showed MIC values with clinical relevance (≤ 1000 μg mL-1) against five strains (P. aeruginosa ATCC 27853, E. coli ATCC 25922, S. aureus ATCC 25923, S. aureus ATCC 29213, and C. krusei). The complex outperformed the ligand demonstrated by antimicrobial activity against four additional ATCC strains (S. epidermidis, E. faecalis, C. albicans, and C. parapsilosis) and clinical isolates (Escherichia, Staphylococcus, and Candida genus). Moreover, the complex showed a harmful effect in human osteosarcoma (MG-63, IC50 = 41.8 ± 6.5 μM) and human lung carcinoma (A549, IC50 = 37.5 ± 6.7 μM) cell lines with a concentration-dependent behavior from 10 to 100 μM. Conclusions. Overall, the complexation with Cu(II) and bipy improved the pharmacological properties of SDZ, which resulted in a promising strategy for developing novel antitumoral or antimicrobial agents with an acceptable safety profile.