Title : Synthesis and cytotoxicity studies on novel piperazinylacetamides
Cancer, characterized by uncontrolled cell growth, causes the death of about 7 million patients each year. Malignant cells can spread all over the body through the lymphatic and the circulatory systems. Side effects of chemotherapeutic drugs being used for cancer treatment affect patients' quality of life negatively. In addition, resistance to cancer chemotherapy often develops. Therefore, the need for new therapeutic agents is increasing day by day (Deng et al., 2015).
In this study, novel compounds, bearing N-[2-(4-substitutedpiperazine-1-yl)acetyl]-N’-[bis-(4-fluorophenyl)methyl]piperazine structures were synthesized. In vitro cytotoxic activities were screened in comparison with camptothecin (positive control) and 5-fluorouracil (reference).
To obtain starting compound, 1-[4-bis(4-fluorophenyl)methyl]piperazine was N-acetylated with chloroacetyl chloride. Target compounds were gained after substitution of N-acetyl chloride group by various piperazine derivatives.
Physical properties of the synthesized compounds were determined and their structures were confirmed by using spectral methods (UV, IR, 1H-NMR, 13C-NMR, Mass spectrometry) and elemental analyses. In addition, their cytotoxic properties were evaluated in vitro by NCI-60 Sulforhodamine B (SRB) assay against human cancer cell lines, Huh7 (hepatocellular), MCF7 (breast) and HCT116 (colorectal).
According to the activity data, most of the compounds are more cytotoxic than 5-fluorouracil against hepatocellular (Huh7) and colorectal (HCT116) cancer cell lines. However, in breast (MCF-7) cancer cell line, all benzhydrylpiperazine derivatives are less cytotoxic than 5-fluorouracil (5-FU). The most active compound for Huh7 cell line is m-methoxyphenyl derivative (compound 5; GI50 = 7.04 µM), and the most active compound against colorectal (HCT-116) cancer cell line is p-chlorophenyl derivative (compound 1; GI50 = 4.36 µM).
Audience take away:
• Piperazine is an extensively studied heterocycle in drug discovery studies. By this presentation, it is aimed to share current research on benzhydrylpiperazine derivatives.
• The audience is expected to use the information on drug discovery studies for cancer.