期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 34, 期 1, 页码 532-546出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2018.1564046
关键词
Pyrazolo[3,4-d]pyrimidines; design; synthesis; anticancer activity; EGFR; ErbB2; caspase-3; cell cycle arrest profile; apoptosis
A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC50 = 1.74 mu M. It also exhibited promising potent anticancer activity against ACHN cell line with IC50 value 5.53 mu M, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC50 = 4.44 mu M) was 1.9-fold more potent than Erlotinib. It inhibited EGFR and ErbB2 kinases at sub-micromolar level (IC50 = 0.18 and 0.25 mu M, respectively). Dual inhibition of EGFR and ErbB2 caused induction of apoptosis which was confirmed by a significant increase in the level of active caspase-3 (11-fold). It showed accumulation of cells in pre-G1 phase and cell cycle arrest at G2/M phase.
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