Treatment of cancer and bacterial diseases represents one of the biggest challenges of modern medicine. We are exposed to numerous cancerogenic factors, wich can lead to genetic mutations and cancerous transformation of cells. Their signiture characteristics are uncontrolled cell growth or immortality, changes in cell cycle regulation, ability to develop new veins in tumour and invasion in other tissues. The main goal of cancer treatment is to entirely destroy or remove tumour tissue without the major effect on healthy cells. The biggest issues with antibacterial drugs are development of bacterial resistance due to incorrect usage of those drugs and the selectivity between human and bacterial cells. With new discoveries available, there are more posibilities of finding new targets and developement of new drugs that would provide greater selectivity and safety.
At the Faculty of pharmacy they develop and synthetisize potencial anticancer and antibacterial drugs. Hsp90 and human topoisomerase IIα are involved in numerous processes in cell growth regulation and represent an important target in cancer therapy. Synthesis of more selective inhibitors is possible, because both of this targets are more expressed in cancer cells. Bacterial topoisomerase IV and DNA-gyrase B existc only in bacterial cell. Inhibitors of those enzymes are highly selective because they don't affect human cells.
In this thesis we wanted to evaluate the effect of selected Hsp90 inhibitors and human topoisomerase IIα as a potencial anticancer drugs and inhibitors of bacterial topoisomerase IV and DNA-gyrase B as a potencial antibacterial drugs on cell proliferation. Main goal of evaluation of anticancer drugs is to prove their cytotoxic effect on cancer cells. With determination of antiproliferative effect of antibacterial drugs we wanted to evaluate their safety. As an in vitro model we used breast cancer cell line (MCF-7). For determination of antiproliferative characteristics, we used MTS viability assay. With preliminary tests we selected drugs wich in concentration 50 µM inhibit the cell viability for at least 60 %. Those drugs were further tested in wider concentration range. With this we determined the relation between concentration and inhibinatory effect and the drug concentration wich inhibits cell viability for half (IC50).
Out of all tested drugs 16 showed appropriate inhibitory activity, ten of them were anticancer and six were antibacterial. For better drugs evaluation we should use other cell lines that would prove the information about the selectivity of those inhibitors. Our results will represent a good basis for furher testings and synthesis of new inhibitors.
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