Synthesis and anticancer activity of some pyrimidine derivatives with aryl urea moieties as apoptosis-inducing agents

被引：40
作者：
Kilic-Kurt, Zuhal [1 ]
Ozmen, Nuri [2 ]
Bakar-Ates, Filiz [2 ]
机构：
[1] Ankara Univ, Fac Pharm, Dept Pharmaceut Chem, Ankara, Turkey
[2] Ankara Univ, Fac Pharm, Dept Biochem, Ankara, Turkey
来源：
BIOORGANIC CHEMISTRY | 2020年 / 101卷
关键词：
Pyrimidines; Urea; Anticancer; Apoptosis mechanism; Synthesis; BCR-ABL; KAPPA-B; DESIGN; INHIBITOR; POTENT; DISCOVERY; TARGETS; GROWTH; AURORA;
D O I：
10.1016/j.bioorg.2020.104028
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A new series of pyrimidine derivatives containing aryl urea moieties was designed and synthesized. The an-ticancer activities of all compounds were evaluated in vitro against colon and prostat cancer cell lines by MTT assay. Among these compounds, 4b exhibited the highest cytotoxic activity against SW480 cancer cell line with IC50 value of 11.08 mu M. Mechanistic studies showed that compound 4b arrested cell cycle at G2/M phase and induced apoptosis through upregulating Bax, Ikb-alpha and cleaved PARP and downregulating Bcl-2 expression levels. Moreover, compound 4b induced loss of mitochondrial membrane potential in SW480 cells. These results suggest that pyrimidine with urea moieties could be a template for designing new anticancer agents.
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页数：10
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