Evaluation of New Antimicrobial Agents Based on tris (1 H -Indol-3-yl)methylium Salts: Activity, Toxicity, Suppression of Experimental Sepsis in Mice

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 2; p. 118
• Main Authors: Trenin, Alexey S, Isakova, Elena B, Treshchalin, Michael I, Polozkova, Vasilisa A, Mirchink, Elena P, Panov, Alexey A, Simonov, Alexander Y, Bychkova, Olga P, Tatarskiy, Victor V, Lavrenov, Sergey N
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.01.2022; MDPI
• Subjects: Antibiotics; Antimicrobial agents; Bacteria; Chloride; Cytotoxicity; Drug dosages; Drug resistance; Experiments; Fungi; Glucose; Gram-negative bacteria; Gram-positive bacteria; Laboratory animals; Multidrug resistant organisms; overcoming of drug resistance; Sepsis; staphylococcal sepsis; toxicity in vitro and in vivo; tris(1H-indol-3-yl)methylium; turbomycin; United States > US; overcoming of drug resistance; staphylococcal sepsis; tris(1H-indol-3-yl)methylium; toxicity in vitro and in vivo; turbomycin
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15020118

The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing (1 -indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13-1.0 µg/mL) against bacteria that were either sensitive or resistant to antibiotics, including multidrug-resistant clinical isolates. The derivatives combining high antimicrobial activity with relatively low cytotoxicity against human donor fibroblasts HPF-hTERT were subjected to further testing on mice. In vivo they revealed fairly good tolerance and relatively low toxicity. Acute toxicity was evaluated, and the main indicators of toxicity, including LD and LD , were determined. A study of compounds in vivo showed their efficiency in the model of staphylococcal sepsis in mice. The efficiency of compounds may be due to the ability of indolylmethylium salts to form pores in the cytoplasmic membrane of microbial cells and thereby facilitate the penetration of molecules into the pathogen.