Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities
Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities
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DOI：
10.1111/cbdd.12929
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发表时间：
2017-07-01
影响因子：
3
通讯作者：
Ragab, Hanan M.
中科院分区：
文献类型：
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作者：
Abd El Razik, Heba A.;Mroueh, Mohamad;Ragab, Hanan M.
本研究报道了两种新型嘌呤生物同位体的合成，它们由吡唑[3,4-d]嘧啶支架通过不同的酰胺键与哌嗪部分相连。研究了新合成的化合物对MDA-MB-231、MCF-7、SF-268、B16F-10等4种细胞系的抗癌活性，以及对脂多糖（LPS）激活的大鼠单核细胞环氧化酶（COX-2）蛋白表达的抑制作用。结果表明，大多数化合物对至少一种细胞系具有中高的细胞毒活性，其中化合物10b对所有细胞系的IC50值为5.5 ~ 11 μ g/ml，与顺铂相当。此外，与对照非刺激细胞相比，其中6种化合物（7b、10a-d和12c）在低浓度（25 μ g/ml）下表现出对LPS诱导的COX-2蛋白表达的抑制作用，并显示出与双氯芬酸钠相当的COX-2选择性指数范围。综上所述，许多吡唑嘧啶衍生物在不同剂量下具有体外抗炎和抗癌活性，其中最具活性的化合物将进行体内药理学评价。
This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d] pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, SF-268, B16F-10) and cyclooxygenase (COX-2) protein expression inhibition in lipopolysaccharide (LPS) activated rat monocytes. The results revealed that most of the synthesized compounds showed moderate to high cytotoxic activity against at least one cell line, with compound 10b being the most active against all used cell lines (IC50 values 5.5-11 mu g/ml) comparable to cisplatin. In addition, six of these compounds (7b, 10a-d, and 12c) demonstrated inhibition of LPS induced COX-2 protein expression at low concentration (25 mu g/ml) as compared to the control non stimulated cells and showed a COX-2 selectivity index range comparable to diclofenac sodium. The overall results indicate that many of these pyrazolopyrimidine derivatives possess in vitro anti inflammatory and anticancer activities at varying doses, and the most active compounds will be subjected to in vivo pharmacological evaluation.