Evaluation of the Potential Anticancer Activity of Pyrazole-Acridine Derivative Synthesis on SKBR-3 Human Breast Cancer Cell Line PİRAZOL-AKRİDİN TÜREVİ SENTEZİNİN SKBR-3 İNSAN MEME KANSERİ HÜCRE HATTINDA POTANSİYEL ANTİKANSER AKTİVİTESİNİN DEĞERLENDİRİLMESİ

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KÜÇÜKBAĞRIAÇIK Y., DASTOURİ M., Elmusa M., Elmusa F., YILMAZ Ö. H., Kasımoğulları R.

Journal of Kirikkale University Faculty of Medicine, cilt.26, sa.1, ss.76-85, 2024 (Scopus, TRDizin)

Özet

Objective: Among heterocyclic compounds with anticancer activity, derivatives of pyrazole containing two nitrogen atoms and acridine containing one nitrogen atom have shown promising results in the treatment of cancer, neurological disorders, and infectious diseases. The main objective of this study is to investigate the anticancer activity of the synthesized pyrazole and acridine compound, particularly on human breast cancer (SKBR-3) cells. Material and Methods: In this study, pyrazole-4-carbaldehyde was obtained based on hydrazone (HT) synthesized using 2-hydrazinobenzothiazole and 4-chloroacetophenone. Pyrazole-4-carbaldehyde was converted to a new pyrazole-acridine derivative (3-ACH) by cyclization using 5,5-dimethylcyclohexane-1,3-dione and 4-nitroaniline. 3-ACH was characterized using Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, Mass Spectrometry, and elemental analysis. The cytotoxic effects of 3-ACH on SKBR-3 cells were evaluated using the cell viability test at different doses (50, 100, and 150 μg/mL) and durations (12 and 24 hours). Additionally, the synthesis of BAX, Caspase-3, Caspase-8, and Caspase-9 apoptotic pathways was examined through immunostaining after 3-ACH application. Results: We demonstrated that 3-ACH exhibits cytotoxic effects on human breast cancer cells, and these effects are dose and duration-dependent. The synthesis increase of Caspase-9 and BAX responsible for intrinsic pathways and Caspase-8 responsible for extrinsic pathways was shown through immunostaining. Moreover, the protein synthesis of Caspase-3, responsible for both intrinsic and extrinsic pathways, significantly increased. Conclusion: These findings suggest that 3-ACH may contribute to its cytotoxic effects by activating both intrinsic and extrinsic apoptotic pathways. The results of our study provide strong evidence for considering 3-ACH as a promising agent for cancer treatment. Further research is needed to understand the role of 3-ACH in the apoptotic response in more detail.