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Rak prostate jedan je od najučestalijih vrsta raka te je i dalje teško izlječiv. Stoga se razvijaju i istražuju novi spojevi koji pokazuju dobra antitumorska svojstva. Imidazolijevi spojevi su heterocikličke aromatske strukture s brojnim farmakološkim učincima među kojima je i antitumorsko, a postižu ga kroz različite načine djelovanja i stanične mete. U ovom radu ispitan je citotoksični učinak novosintetiziranih imidazolijevih spojeva, hidroksiimino-metil imidazolijevih bromida IV, VI, VII i X testovima in vitro na stanice raka prostate PC-3. Inhibitorni učinak na vijabilnost stanica ispitan je praćenjem aktivnosti mitohondrijske sukcinat dehidrogenaze u metabolički aktivnim stanicama. Zatim je ispitano narušavaju li ispitivani spojevi integritet stanične membrane mjerenjem aktivnosti enzima laktat dehidrogenaze (LDH). Konačno, metodom protočne citometrije istraženo je induciraju li ispitivani spojevi programiranu staničnu smrt, apoptozu. Spojevi VII i X pokazali su najveći inhibitorni učinak na vijabilnost stanica te značajno otpuštanje LDH u medij, što ukazuje na indukciju nekroze. S druge strane, niti jedan od spojeva nije inducirao apoptozu, stoga bi ispitani spojevi trebali biti modificirani kako bi bili pogodni za daljnja za daljnja ispitivanja kao potencijalni antitumorski lijekovi. Prostate cancer is one of the most common types of cancer and is still difficult to cure. Therefore, new compounds that show good anticancer properties are being developed and studied. Imidazolium compounds are heterocyclic aromatic structures with numerous pharmacological effects, including anticancer, which is achieved through different modes of action and cellular targets. In this work the cytotoxic effect of newly synthesized imidazole compounds, hydroxyimino-methyl imidazolium bromide IV, VI, VII and X on PC-3 prostate cancer cells was examined in vitro. The inhibitory effect on cell viability was examined by measuring mitochondrial succinate dehydrogenase activity in metabolically active cells. The loss of cell membrane integrity is then examined by measuring the activity of the enzyme lactate dehydrogenase (LDH). Finally, flow cytometry was performed to investigate whether the tested compounds induce programmed cell death, apoptosis. Compounds VII and X showed the greatest inhibitory effect on cell viability and significant release of LDH into the medium, indicating induction of necrosis. On the other hand, none of the compounds induced apoptosis, therefore the tested compounds should be modified to be suitable for further testing as potential antitumor drugs. |
