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Cytotoxic and apoptotic effects of novel pyrrolo[2,3-d]pyrimidine derivatives containing urea moieties on cancer cell lines.
Anti-cancer Agents in Medicinal Chemistry 2018 June 5
A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized and evaluated for their anticancer activity against cancer cell lines including A549, PC3, SW480 and MCF-7. Among the synthesized compounds, 9e, 10a and 10b exhibited the most potent cytotoxic activities against different cancer cell lines. Compound 10a (IC50 = 0.19 µM) was found to be the most potent derivative against PC3 cells. Compound 10b and 93 showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 µM and 4.55 µM, respectively.Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. .Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway.
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