Ahmet O. Görgülü

Synthesis, docking studies, in vitro cytotoxicity evaluation and DNA damage mechanism of new tyrosine‐based tripeptides

AbstractPeptides are one of the leading groups of compounds that have been the subject of a great deal of biological research and still continue to attract researchers' attention. In this study, a series of tripeptides based on tyrosine amino acids were synthesized by the triazine method. The cytotoxicity properties of all compounds against human cancer cell lines (MCF‐7), ovarian (A2780), prostate (PC‐3), and colon cancer cell lines (Caco‐2) were determined by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide assay method, and % cell viability and logIC50 values of the compounds were calculated. Significant decreases in cell viability were observed in all cells (p < 0.05). The comet assay method was used to understand that the compounds that showed a significant decrease in cell viability had this effect through DNA damage. Most of the compounds exhibited cytotoxicity by DNA damage mechanism. Besides, their interactions between investigated molecule groups with PDB ID: 3VHE, 3C0R, 2ZCL, and 2HQ6 target proteins corresponding to cancer cell lines, respectively, were investigated by docking studies. Finally, molecules with high biological activity against biological receptors were determined by ADME analysis.

Synthesis of New Cinnamoyl‐Amino Acid Conjugates and in Vitro Cytotoxicity and Genotoxicity Studies

AbstractAmino acid conjugates are described by the reaction of amino acids with bioactive organic groups such as vitamins, hormones, flavonoids, steroids, and sugars. In this study, 12 new conjugates were synthesized by reaction of cinnamic acid derivatives with various amino acids. Cytotoxic studies against four different human cancer cells (MCF7, PC‐3, Caco‐2, and A2780) were carried out by MTT assay method at five different concentrations. The structure‐activity relationships based on the cell viability rates were evaluated. To compare the anticancer activities of the compounds using computational chemistry methods, they were docked against A2780 human ovarian cancer, Michigan Cancer Foundation‐7 (MCF7), human prostate cancer (PC‐3) and human colon epidermal adenocarcinoma (Caco‐2) cell lines and compared with the standard 5‐Fluorouracil. The results indicate that the efficacy of cinnamic acid derivatives increases with the presence of amino acids. Comet assay was conducted to understand whether the cell deaths occur through DNA damage mechanism and the results exhibit that the changes in the specified parameters were statistically significant (p<0.05). Our study demonstrated that the compounds cause cell death through the formation of DNA damage mechanism.