Synthesis and in vitro antiproliferative activity of novel pyrazolo[3,4-d]pyrimidine derivatives

被引：8
作者：
Abdou, Nermin S. [1 ]
Serya, Rabah A. T. [1 ]
Esmat, Ahmed [2 ]
Tolba, Mai F. [2 ,3 ]
Ismail, Nasser S. M. [1 ]
Abouzid, Khaled A. M. [1 ]
机构：
[1] Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt
[2] Ain Shams Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo 11566, Egypt
[3] Amer Univ Cairo, Sch Sci & Engn, Dept Biol, New Cairo, Egypt
来源：
MEDCHEMCOMM | 2015年 / 6卷 / 08期
关键词：
RECEPTOR TYROSINE KINASES; INHIBITORS; DESIGN; POTENT; CYTOTOXICITY; PYRIMIDINES; ANTAGONISTS; CYCLINS; ANALOGS; ASSAY;
D O I：
10.1039/c5md00127g
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 novel series of pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity. Among the five compounds selected by NCI, compound 11a showed a distinctive pattern of selectivity on cell line panels and was further screened for a 5-log dose range, where it showed potent antiproliferative activity with median growth inhibition (GI(50)) equal to 1.71 mu M against the CNS cancer SNB-75 cell line. The tested derivative showed remarkably the highest cell growth inhibition against non-small cell lung cancer HOP-62, CNS cancer SNB-75, breast cancer HS578T, and melanoma MALME-3M cell lines. Flow cytometric analysis revealed that compound 11a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. Further investigation showed that compound 11a induced significant cell cycle arrest at G0/G1 phase partly due to its ability to downregulate cyclin D1 and upregulate p27(kip1) levels.
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收藏
页码：1518 / 1534
页数：17
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