Investigation of in vitro and in vivo effects of novel amino acid conjugates against breast cancer

Today, cancer ranks first in the classification of deadly diseases. Breast cancer is one of the most common types of cancer in our country and around the world. Due to the negative side effects of chemotherapeutic agents used in cancer treatment and adopted as a traditional treatment approach, the development of agents without side effects has gained importance. Our thesis is based on the principle that the most effective compound was selected as a result of the molecular docking (in silico) analyzes of the two anticarcinogen activity candidate substances we produced and the analysis of breast cancer cell lines (in vitro), and the application of this substance at the appropriate dose (in vivo) on female rats with breast cancer. Cell viability and cell proliferation analyzes of synthesized glycine-containing hydroxy cinnamic acid conjugate (HCA-Gly-OCH3) and coumarin-containing cysteine amino acid conjugate (Cys-PA-N3-Kum) compounds were performed in vitro. As a result of cell culture analysis, Cys-PA-N3-Kum compound was determined to be a more effective anticarcinogenic activity candidate. This compound was then administered on DMBA-induced Wistar albino female rats. In order to control the synthesized compound, Tamoxifen, which is also used in the clinic, was also applied on experimental animals. After the animal experiments of the study, molecular biological and histopathological analyzes were performed. In addition to the MDA, GSH, CAT activities of the groups, necessary analyzes were also performed to determine the level of DNA damage in the groups. In addition, the level of p53, COX-2, HER2 and TNF-α protein expressions was determined by Western blot method. In general, it was observed that MDA levels decreased, while CAT and GSH levels increased in the treatment groups. It was determined that COX-2, HER2 and TNF-α protein expressions decreased in the treatment groups, while p53 protein expression increased. In the histopathological analyzes performed to determine tumor size and typing, it was determined that invasive tumors were more common in damage groups, and a decrease in tumor formation and size reduction in amino acid conjugate and tamoxifen groups. In in silico analysis, when all data such as proximity to the active site of the macromolecule, interacting residues, bond types, estimated Ki's, docking scores are evaluated together, it has been revealed that the conjugate may be more effective on HER2 and p53. In line with the results obtained, it is understood that the Cys-PA-N3-Kum conjugate has protective effects against breast cancer and this substance has promising results for future studies.