Synthesis and Antiproliferative Evaluation of New Pyrimido[1,6-a]Thieno[2,3-d]Pyrimidine Derivatives

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• 作者：Hoda Atapour-Mashhad ; Mohammad Soukhtanloo ; Abdolhossien Massoudi ; Ali Shiri ; Seyed Mohamadreza Parizadeh and Mehdi Bakavoli
• 刊名：Journal of Heterocyclic Chemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：54
• 期：1
• 页码：366-374
• 全文大小：3309K
• ISSN：1943-5193

文摘

A facile one-pot synthesis of new pyrimido[1,6-a]thieno[2,3-d]pyrimidin-4-ones jhet2592-eo-0005" rel="references:#jhet2592-eo-0005"> ,jhet2592-eo-0006" rel="references:#jhet2592-eo-0006"> is reported via base-catalyzed reaction of 2-amino-3-cyanothiophenes jhet2592-eo-0001" rel="references:#jhet2592-eo-0001"> ,jhet2592-eo-0002" rel="references:#jhet2592-eo-0002"> with Math/MathML" id="jhet2592-eo-0003">2,4-dichloro-5-bromo-6-methylpyrimidine jhet2592-eo-0003" rel="references:#jhet2592-eo-0003">. Subsequent treatment of the products with several amines under a mild condition gave a host of the new amino derivatives jhet2592-eo-0008" rel="references:#jhet2592-eo-0008 #jhet2592-eo-0009 #jhet2592-eo-0010 #jhet2592-eo-0011 #jhet2592-eo-0012 #jhet2592-eo-0013 #jhet2592-eo-0014 #jhet2592-eo-0015 #jhet2592-eo-0016 #jhet2592-eo-0017 #jhet2592-eo-0018 #jhet2592-eo-0019">. The target compounds were evaluated for antiproliferative activity by an 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay on human breast cancer (MCF-7) and mouse fibroblast nonmalignant (L929) cell lines. The activation was structural, concentration, and time dependent. Doses inducing 50% cell-growth inhibition (IC₅₀) for compounds jhet2592-eo-0005" rel="references:#jhet2592-eo-0005"> ,jhet2592-eo-0006" rel="references:#jhet2592-eo-0006"> and jhet2592-eo-0008" rel="references:#jhet2592-eo-0008 #jhet2592-eo-0009 #jhet2592-eo-0010 #jhet2592-eo-0011 #jhet2592-eo-0012 #jhet2592-eo-0013 #jhet2592-eo-0014 #jhet2592-eo-0015 #jhet2592-eo-0016 #jhet2592-eo-0017 #jhet2592-eo-0018 #jhet2592-eo-0019"> against MCF-7 cells were explored. Compounds jhet2592-eo-0013" rel="references:#jhet2592-eo-0013"> and jhet2592-eo-0019" rel="references:#jhet2592-eo-0019"> as the two most potent analogs induced a sub-G1 peak in the flow-cytometry histogram of treated cells, compared with control, indicating that apoptotic cell death is involved in compound jhet2592-eo-0013" rel="references:#jhet2592-eo-0013">-induced and compound jhet2592-eo-0019" rel="references:#jhet2592-eo-0019">-induced toxicity. Compounds jhet2592-eo-0013" rel="references:#jhet2592-eo-0013"> and jhet2592-eo-0019" rel="references:#jhet2592-eo-0019"> exerted cytotoxic and proapototic effects on MCF-7 cell line.