Study of the Activity and Toxicity of New Antibacterial Agents Based on Triindolylmethane Derivatives in vivo

Abstract

Biological properties of new synthetic triindolylmethylium antibiotics of the triindolylmethane group, including compounds containing a maleimide fragment in the structure, are studied. Their high antibacterial activity in vitro, mainly against gram-positive bacteria, but also against strains with multiple drug resistance, was shown. The compounds, that showed the least in vitro toxicity on human donor fibroblasts PF-hTERT, were subjected to further testing in animals (mice). The LD50 and LD10 values identified were 24.2 and 16.9 mg/kg, respectively, for LCTA-2701 compound and 41.8 and 34.1 mg/kg for LCTA-2841 compound. In vivo testing of chimeric compounds showed their high efficiency in the model of staphylococcal sepsis in mice and a fairly good tolerability. ED50 values were 1.09 mg/kg for LCTA-2701 compound and 18.27 mg/kg for LCTA-2841 compound, and their chemotherapeutic index was, respectively, 22.2 and 2.3.

Keywords

• triindolylmethane
• maleimide
• chimeric (hybrid) antibiotics
• antibacterial and antifungal activity in vitro and in vivo
• cytotoxicity
• in vivo toxicity
• efficacy in a model of staphylococcal sepsis in mice