2. Academic Validation
  3. Discovery of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purines containing a carboxamide moiety as potential selective anti-lung cancer agents

Discovery of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purines containing a carboxamide moiety as potential selective anti-lung cancer agents

  • Eur J Med Chem. 2018 May 10:151:327-338. doi: 10.1016/j.ejmech.2018.03.084.
Tao-Qian Zhao 1,  Yuan-Di Zhao 1,  Xin-Yang Liu 1,  Bo Wang 1,  Zhong-Hua Li 1,  Zhang-Xu He 1,  Xin-Hui Zhang 1,  Jian-Jia Liang 1,  Li-Ying Ma 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China.
  • 2 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
  • 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: maliying@zzu.edu.cn.
PMID: 29635165 DOI: 10.1016/j.ejmech.2018.03.084
Abstract

A new series of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purine-8-caboxamide derivatives were designed, synthesized, and further evaluated for their antiproliferative activities on four human Cancer cell lines (A549, MGC803, PC-3 and TE-1). The structure-activity relationships (SARs) studies were conducted through the variation in the two regions, which including position 8 and 9, of purine core. One of the compounds, 8, containing a terminal piperazine appendage with a carboxamide moiety at position 8 and phenyl group at position 9 of 6-chloro-8,9-dihydro-7H-purine core, showed the most potent antiproliferative activity and good selectivity between Cancer and normal cells (IC50 values of 2.80 μM against A549 and 303.03 μM against GES-1, respectively). In addition, compound 8 could inhibit the colony formation and migration of A549 cells in a concentration-dependent manner, as well as induce the Apoptosis possibly through the intrinsic pathway.

Keywords

6-Chloro-purine-8-carboxamide; Antiproliferative activity; Apoptosis; Migration.

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