1. Design, synthesis and preliminary biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids as antiproliferative agents.
- Author
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Li, Zhong-Hua, Liu, Xue-Qi, Zhao, Tao-Qian, Geng, Peng-Fei, Guo, Wen-Ge, Yu, Bin, and Liu, Hong-Min
- Subjects
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PYRIMIDINE derivatives , *ANTINEOPLASTIC agents , *LUNG cancer , *HETEROARENES , *APOPTOSIS , *CANCER cells , *THIOUREA - Abstract
A series of new [1,2,3]triazolo[4,5- d ]pyrimidine/thiourea hybrids were designed and synthesized through the scaffold replacement/ring cleavage strategy. SARs studies revealed that the N -heteroarene moiety attached to the thiourea is preferred over the phenyl ring for the R 2 substituents, while the hydrophobic aromatic group is beneficial for improving the activity. Among these compounds, compound 5r significantly inhibited cell growth of lung cancer cell lines H1650 and A549 (IC 50 = 1.91, 3.28 μM, respectively), but was less toxic against the normal cell line GES-1 (IC 50 = 27.43 μM). Mechanistic studies showed that compound 5r could remarkably inhibit the colony formation of H1650 cells, induced apoptosis possibly through the intrinsic apoptotic pathways, and arrested the cell cycle at G2/M phase. Our studies suggest that the [1,2,3]triazolo[4,5- d ]pyrimidine/thiourea hybrids are a new class of chemotypes possessing interesting antiproliferative activity against lung cancer cells and could be potentially utilized for designing new antitumor agents. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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