Investigations of Oral Pathogens on Copper(II) Complexes with Thiosemicarbazone: Antimicrobial and Antibiofilm Activities in Addition to in vitro and in vivo Toxicity

Abstract

Oral caries is a major global public health issue involving complex biofilm interactions and contributing to several systemic conditions. Metallic compounds have gained attention as antimicrobial agents due to their notable antibacterial activity. In this work, we investigated the anticariogenic potential of two copper(II) complexes containing Schiff base ligands, namely [CuCl(atc-Me)] (1, atc-Me = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone) and [{Cu(μ atc Me)}₂μ-SO₄] (2). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC₅₀), and synergistic activity with chlorhexidine were evaluated. The in vivo toxicity of the complexes was further assessed using Caenorhabditis elegans. MBC values indicated a bactericidal effect for both complexes. Synergistic activity with chlorhexidine was observed against Streptococcus mutans and Enterococcus faecalis strains. Cytotoxic evaluation in human fibroblast cultures revealed that complexes 1 and 2 showed half maximal inhibitory concentration (IC₅₀) values of 2.9 and 4.9 µg mL^-1, respectively. Toxicity assays in C. elegans showed lethal concentration (LC₅₀) values approximately three times higher than the MIC values for complexes 1 and 2: Molecular docking analyses revealed favorable binding energy values between the copper complexes and bacterial proteins. Overall, this investigation suggests an alternative approach for anticariogenic treatment, highlighting significant antibiofilm activity combined with low toxicity.

Keywords:
copper complexes; thiosemicarbazone; oral pathogens; antibiofilm activity; cytotoxicity