Experimental Determination of the “Therapeutic Window” of the Synthetic Peptidomimetic SAMP-1

Antibiotic resistance has been recognized by WHO as one of the three most important public health threats of the 21st century. Thus, the search for new alternative antimicrobial molecules is an urgent public health problem throughout the world. A synthetic antimicrobial peptidomimetic SAMP-1 has been created, which interacts through electrostatic forces with the membrane of microbial bodies, causing perforation of the membrane and loss of electrolytes, leading to the death of prokaryotes. SAMP-1 showed itself in microbiological studies as an active substance against certification strains of bacteria and fungi. To determine the parameters of acute toxicity, two types of rodents were used: mice and rats. Using a single intravenous injection of the study substance in various doses, and then 14 days of daily observation. The toxic dose range for mice was found to be 7.5-10 mg/kg and for rats 4.5-5.5 mg/kg. SAMP-1 demonstrates a dose-dependent lethal effect. After 14 days, the animals were euthanized and no signs of toxic effects were detected on macropreparations. Animals that died during the experiment had signs of distributive shock upon macroscopy. It was found that for SAMP-1 the “therapeutic window” has the following values: 0.1 - 7.0 mg/kg for mice and 0.1-4.0 mg/kg for rats. Calculated semi-lethal doses are 8.88 mg/kg in mice; 4.63 mg/kg in rats. Based on the toxicity results, there is a need for the next stage of research on SAMP-1 in cell culture, for a more detailed study of the interaction with the eukaryotic membrane.