Antibacterial agents are compounds that are used to treat bacterial infections due to their bactericidal or bacteriostatic action. They work based on the principle of selective toxicity which is possible due to differences between bacterial and host cells. The lowest concentration of the antimicrobial agent that inhibits the growth of microorganisms is defined as the minimum inhibitory concentration. Based on their origin, antibacterial agents are divided into antibiotics and chemotherapeutics, but they can also be divided according to characteristics of their molecular structure and their spectrum of treatment. Antibacterial agents work according to five main mechanisms of action, but due to their increasingly extensive and improper use, some bacteria have adapted to them and developed resistance. Bacterial resistance is a phenomenon where bacteria are able to survive and grow despite exposure to an antibacterial agent that would otherwise be lethal to their survival. The constant search and development of new active substances that would replace existing active substances to which bacteria have developed resistance is of utmost importance. Compound library screening is one of the methods of antibacterial compound discovery.
In this master's thesis, we evaluated the antibacterial activity of various compounds from the compound library of the Faculty of Pharmacy University of Ljubljana. First we assessed the biological activity of the compounds on the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli. Then we determined the minimum inhibitory concentration (MIC) of six out of 862 tested compounds that showed an inhibitory effect on the growth of bacteria. Compounds 2D4, 3D6, 8C4, 9F3 and 11F1 showed inhibitory action on the growth of Staphylococcus aureus. Compound 3A1 showed an inhibitory effect on the growth of Escherichia coli. The determined MIC for compounds 2D4, 3D6, 8C4 and 3A1 is 25 μmol/L, and the determined MIC for compounds 9F3 and 11F1 is 6,25 μmol/L. We also observed the structure-activity relationship for the six active compounds. After a literature review we found that compounds 2D4, 3A1, 3D6 and 11F1 are structurally similar to already known compounds with antibacterial activity, while compounds 8C4 and 9F3 do not show similarity to any known antibacterial compound. They represent new chemotypes, which with further optimization, could be used for the development of new antibacterial agents.
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