2. Academic Validation
  3. Design, synthesis and preliminary biological evaluation of 5,8-dihydropteridine-6,7-diones that induce apoptosis and suppress cell migration

Design, synthesis and preliminary biological evaluation of 5,8-dihydropteridine-6,7-diones that induce apoptosis and suppress cell migration

  • Eur J Med Chem. 2018 Jan 1:143:1959-1967. doi: 10.1016/j.ejmech.2017.11.009.
Peng-Fei Geng 1,  Cong-Cong Wang 1,  Zhong-Hua Li 1,  Xiao-Ning Hu 1,  Tao-Qian Zhao 1,  Dong-Jun Fu 1,  Bing Zhao 1,  Bin Yu 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China.
  • 2 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China. Electronic address: zzuyubin@hotmail.com.
  • 3 Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China. Electronic address: liuhm@zzu.edu.cn.
PMID: 29133051 DOI: 10.1016/j.ejmech.2017.11.009
Abstract

Pteridines are an important class of fused heterocycles found in Natural Products and drug molecules, and have shown diverse biological activities. A focused library of 5,8-dihydropteridine-6,7-dione derivatives were designed and evaluated for their antiproliferative activity against MGC-803, SGC-7901, A549 and PC-3 Cancer cell lines. The SARs studies highlighted the importance of the piperazine substituted 5,8-dihydropteridine-6,7-dione frameworks for the activity and revealed essential structural elements. Among these compounds, compound 5n displayed the most potent and broad-spectrum antiproliferative inhibition against the tested cell lines and was sensitive to MGC-803 cell line, slightly more potent than 5-FU. Preliminary mechanistic studies showed that compound 5n could inhibit the colony formation and migration of MGC-803 cells. Besides, flow cytometry analysis showed that compound 5n concentration-dependently induced Apoptosis of MGC-803 cells. Our studies suggest that the piperazine substituted 5,8-dihydropteridine-6,7-dione frameworks may be regarded as new chemotypes for designing effective antitumor agents targeting gastric Cancer cells.

Keywords

5,8-Dihydropteridine-6,7-dione; Antiproliferative activity; Apoptosis; Colony formation; Migration.

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