Synthesis and Cytotoxic Evaluation of 2-Pyrazoline Derivative on Leukemia Cancer Cell Line K562
الموضوعات :Masoud Shaabanzadeh 1 , Maryam Bikhof Torbati 2
1 - Department of Chemistry, Damghan Branch, Islamic Azad University, Damghan, Iran
2 - Department of Biology, Yadegar-e-Imam Khomeini (RAH) Shahr-e-Rey Branch, Islamic Azad University, Tehran, Iran
الکلمات المفتاحية: anticancer, Leukemia, 2-Pyrazoline, Indenoquinoxaline, Cytotoxic effect, K562 cell line, PBMC,
ملخص المقالة :
The 2-pyrazoline derivatives have a wide range of biological effects, such as anti-viral, anti-bacterial, anti-fungal, anti-depressant and anti-cancer effects. Studies have shown that compounds containing 2-pyrazoline along with another heterocycles may show more effective biological properties. In this study, a 2-pyrazoline derivative with a spiro-indenoquinoxaline ring at C3 position was synthesized by one-pot microwave-assisted method and its chemical structure was confirmed by 1H NMR spectroscopy. The cytotoxic effects of the compound were evaluated on the K562 cell line and phytohemagglutinin-activated peripheral bloodmononuclear cells (PHA+PBMC) by MTT assay.Additionally, the cytotoxic effects of cisplatin on these cells were investigated and compared with those of 2-pyrazoline. The IC50 values obtained from the 2-pyrazoline derivative effects on the K562 cell line and PHA+PBMC cells were 45 and 55 μg/mL respectively, while cisplatin inhibited proliferation of the same cells with IC50 value 1.71 and 7.8 µg/mL respectively. The results of this study showed that the synthesized derivative had a cytotoxic activity on the K562 cancer cell line at higher concentrations than cisplatin.
1. Torre L.A., Siegel R.L., Ward E.M., Jemal A., 2016. Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Prevent Biomarkers. 25(1), 16-27.
2.Li J.J., 2006 Laughing Gas Viagra and Lipitor: The Human Stories behind the Drugs We Use. Oxford University Press, UK.
3. Takimoto C.H., Calvo E., 2008. Principles of oncologic pharmacotherapy. Cancer management: a multidisciplinary approach. 11, 1-9.
4. Marella A., Ali R., Alam T., Saha R., Tanwar O., Akhter M., Shaquiquzzaman M., Mumtaz Alam M., 2013. Pyrazolines: a biological review. Mini Rev Med Chem. 13(6), 921-931.
5. Bashir R., Ovais, S., Yaseen S., Hamid H., Alam M.S., Samim M., Singh S., Javed K., 2011. Synthesis of some new 1, 3, 5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents. Bioorg. Med Chem Lett. 21(14), 4301-4305.
6. Ciupa A., Paul A., Mahon M.F., Wood P.J., Caggiano L., 2013. Synthesis and antiproliferative activity of some 3-(pyrid-2-yl)-pyrazolines. Med Chem Comm. 4(6), 956-961.
7. Gowramma B., Jubie S., Kalirajan R., Gomathy S., Elango K., 2009. Synthesis, anticancer activity of some 1-(Bis N, N-(Chloroethyl)-amino acetyl)-3, 5-disubstituted 1, 2-pyrazolines. Int J Pharm Tech Res. 1(2), 347-352.
8. Havrylyuk D., Zimenkovsky B., Vasylenko O., Zaprutko L., Gzella A., Lesyk R., 2009. Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur J Med Chem. 44(4), 1396-1404.
9. Khalil N.A., Ahmed E.M., El-Nassan H.B., 2013. Synthesis, characterization, and biological evaluation of certain 1, 3-thiazolone derivatives bearing pyrazoline moiety as potential anti-breast cancer agents. Med Chem Res. 22(2), 1021-1027.
10. Carta A., Piras S., Loriga G., Paglietti G., 2006. Chemistry, biological properties and SAR analysis of quinoxalinones. Mini Rev Med Chem. 6(11), 1179-1200.
11. Santos Bubniak L.D., Gaspar P.C., de Moraes A.C.R., Bigolin A., de Souza R.K., Buzzi F.C., Corrêa R., Filho V.C., Bretanha L.C., Micke G.A., Nunes R.J., 2016. Effects of 1, 3, 5-triphenyl-4, 5-dihydro-1 H-pyrazole derivatives on cell-cycle and apoptosis in human acute leukemia cell lines. Can J Physiol Pharmacol. 95(5), 548-563.
12. Lee H., Cho S., Namgoong K., Jung J.K., Cho J., Yang, S.I., 2004. Synthesis and in vitro evaluation of 7-dialkylaminomethylbenzo [g] quinoxaline-5, 10-diones. Bioorg Med Chem Lett. 14(5), 1235-1237.
13. Huang X.F., Lu X., Zhang Y., Song G.Q., He Q.L., Li Q.S., Yang X.H., Wei Y., Zhu H.L., 2012. Synthesis, biological evaluation, and molecular docking studies of N-((1, 3-diphenyl-1H-pyrazol-4-yl)methyl) aniline derivatives as novel anticancer agents. Bioorg Med Chem. 20(16), 4895-4900.
