Yeni Sentezlenen Benzamit Türevi Molekülün Toksik Etkilerinin Hayvan Modelinde Araştırılması ve Multipl Miyelomlu Farelere Uygulanması

Abstract

Multiple Myeloma (MM) disease continues to be an incurable disease despite improvements in the survival of its patients with the development of new therapeutic agents, and so the search for new drugs that can control the disease continues. In recent years, it has different action mechanisms against MM; New agents such as monoclonal antibodies, proteasome inhibitors, immune modulatory drugs and histone deacetylase inhibitors are being developed, but the approval process of these drugs requires several years of research and large investment. Therefore, as a result of the ongoing search for new potential drugs, results were obtained that N- (2-Hydroxy-4 Nitrophenyl) -4 Ethylbenzamide (XT5), a unique molecule in the structure of benzamide synthesized in the Department of Pharmaceutical Chemistry of Ankara University, can reverse anti-myeloma and drug resistance. has been. In this thesis study, an animal myeloma model was created and studies were conducted to determine the effectiveness and toxicity of the molecule in question, XT5, with an in vivo study. For this purpose, 5 mg / kg, 10 mg / kg and 50 mg / kg doses of XT5 were administered to rats. In order to determine possible toxic effects, histopathological analyzes were made in rat tissues and ALT, AST, Total protein, Urea, Albumin and GGT levels were measured with blood tests, and hematological analyzes were performed in the blood. According to the results of this analysis, no evidence of histopathological damage was found in rats after administration of 5 mg/kg, 10 mg/kg and 50 mg/kg doses of XT5 for one week and eight weeks. As a result of the biochemical and hematological analyzes performed on the blood of rats; It has been shown that there is no significant difference between the XT5 administration groups and the control groups. In order to determine the possible DNA damage caused by the XT5 molecule in rats, the comet method was applied in the blood of rats. According to the results, it was determined that this molecule did not cause genomic toxicity in rats up to 5 mg / kg, 10mg / kg and 50mg / kg levels. In order to determine XT5 activity in NSG mice with multiple myeloma, XT5 applications were performed following tumor formation in mice. Dexamethasone and bortezomib, which are currently used for the treatment of multiple myeloma, were used as the control group. Tumor sizes were monitored by performing bioluminescence imaging intermittently in rats. According to the results, it has been shown that the XT5 molecule does not cause serious toxicity at the dose at which it exerts anti-myeloma effect in vivo. With the support of our findings, different applications of the XT5 molecule in the mouse myeloma model have been opened.