Synthesis, caracterization and in vitro/in vivo/ex vivo investigations of cancer treatment potential of organometalic compounds for hedgehog inhibition in cancer treatment

Repeated growth feature of cancer is regulated by metabolic pathways. However, some metabolic pathways, such as the Hedgehog pathway, play an important role in acquiring abilities such as cancer aggressiveness, invasion, metastasis and recurrence. The Hedgehog metabolic pathway is normally active in the embryonic developmental process and in self-renewing tissues, however it has been identified that a de-regulation of this pathway leads to the cancer formation. In addition, the high activity of the hedgehog metabolic pathway in the cancer stem cell has contributed to the search for inhibitors for this metabolic pathway. In the scope of the doctoral dissertation study, it is aimed to synthesize organometallic compound for the Hedgehog metabolic pathway and its characterization, performing cell culture studies, investigate the treatment potential via xenograft cancer models in nude mice and achieve ex vivo studies. As a result, a cis-4-hydroxyphenylplatinum (II) diamine compound was synthesized with a yield of 62%. The MTT assay on the A549-luc and SKOV3-luc cell lines resulted in IC50 values of 13.44 and 7.91 μM, respectively. Tumor growth continued in the control group when healing was observed in the treatment group with i.v. drug administration in xenograft models.