Investigation of the effect of novel β-lactam derivatives synthesized from substituted phenethylamines on resistance genes of MRSA isolates

The unconscious use of antibiotics, which is one of the most important treatment tools of modern medicine, and the resulting resistance in bacterial isolates is a serious problem. Therefore, the appropriate and correct antibiotic treatment affects the clinical course and prognosis in many infectious diseases. Antibiotics to be selected for the treatment of infectious diseases should be targeted and effective, as well as have minimum toxicity. In this context, β-lactam group antibiotics are the most prescribed drugs due to their broad spectrum of action and minimal toxicity. In the thesis study, new β-lactam derivatives were synthesized with a yield of 41%-91%, and their antibacterial activities were investigated against MRSA isolates, which are the main cause of nosocomial infections. In this regard, firstly, the presence of mecA and blaZ resistance genes in isolates was determined and the antibacterial activities of new β-lactam derivatives against these isolates were determined, and the MIC values of the compounds were measured as 7,8125-15.625 µg/ml. As a result of the antibacterial tests, the compounds numbered (25) and (27) effective against MSSA and MRSA isolates were selected and resistance was established in vitro and the isolates could not develop resistance against these compounds. Then, the role of compounds (25) and (27) against MRSA isolates in the mechanism of resistance were investigated by molecular (qRT-PCR) and biochemical (Nitrocefin) analyses and their effects on resistance genes. As a result of the study, it was observed that the compounds decreased the expression of resistance genes compared to the control. The β-lactamase enzyme in MRSA isolates was determined by nitrocefin analysis, the effects of compounds (25) and (27) on β-lactamase enzyme were investigated, and it was observed that the compounds inhibited the β-lactamase enzyme. In addition, it was observed that the synthesized compounds (25) and (27) had dose-dependent minimum toxicity in two compounds whose cytotoxic properties were investigated on healthy skin cell lines.