Synthesis of a new series of pyrimidine derivatives: exploration of anti-proliferative activity on EAT cells and molecular docking
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- 作者：N. Senthilkumar ; Y. Dominic Ravichandran ; K. M. Kumar…
- 关键词：2 ; Thiouracil ; Ehrlich ascites tumour cell ; Antiproliferative activity ; Casein kinase ; 2 inhibitor ; CK2 ; Binding energy
- 刊名：Research on Chemical Intermediates
- 出版年：2016
- 出版时间：February 2016
- 年：2016
- 卷：42
- 期：2
- 页码：1295-1313
- 全文大小：1,316 KB
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46.K.M. Kumar, P. Anitha, V. Sivasakthi, S. Bag, P. Lavanya, A. Anbarasu, S. Ramaiah, 3 Biotech 4, 241 (2014)CrossRef - 作者单位：N. Senthilkumar (1)
Y. Dominic Ravichandran (1) (3)
K. M. Kumar (2)
Sudha Ramaiah (2)
1. Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore, 632 014, Tamil Nadu, India
3. Department of Science and Humanities, Karpagam College of Engineering, Coimbatore, 641032, Tamil Nadu, India
2. Bioinformatic Division, School of Bioscience and Technology, VIT University, Vellore, 632 014, Tamil Nadu, India - 刊物类别：Chemistry and Materials Science
- 刊物主题：Chemistry
Catalysis
Physical Chemistry
Inorganic Chemistry - 出版者：Springer Netherlands
- ISSN：1568-5675
文摘
A new series of pyrimidine derivatives was designed and synthesized from 2-thiouracil via multicomponent, Biginelli-type reactions and structurally characterized by all spectral means. Synthesized compounds were evaluated for antiproliferative activity against Ehrlich ascites tumour (EAT) cells. A molecular docking study was carried out to establish the binding mode of these compounds into human casein kinase-2 inhibitor (CK2). The established binding modes of these compounds into human CK2 were in very good agreement with the in vitro antiproliferative activity. Compound 4-(2-(1H-indol-2-yl)ethylamino)-2-(2-(diethylamino)ethylthio)-6-(4-fluorophenyl)pyrimidine-5-carbonitrile 4h exhibited stronger cytotoxic activity against EAT cells with an IC50 value of 5.2 µM which was the nearest cytotoxic activity compared with the standard drug methotrexate (MTX) that showed an IC50 value of 3.6 µM. Compound 4h has the maximum cytotoxicity against EAT cell, the lowest binding energy (−8.7 kcal/mol) and good ligand efficiency with CK2 compared to all other compounds.