2. Academic Validation
  3. Design, synthesis and anti-tumor activity studies of novel pyrido[3, 4-d]pyrimidine derivatives

Design, synthesis and anti-tumor activity studies of novel pyrido[3, 4-d]pyrimidine derivatives

  • Bioorg Med Chem Lett. 2022 Nov 15:76:129020. doi: 10.1016/j.bmcl.2022.129020.
Wen-Ge Guo 1,  Jun-Ru Zhao 2,  Min Li 2,  Ting Hu 2,  Zengyangzong Dan 2,  Qian Zhang 2,  Li-Ying Ma 3,  Sai-Yang Zhang 4,  Bing Zhao 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Pharmaceutical Department, Changzhi Medical College, Changzhi 046000, China.
  • 2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 3 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; China Meheco Topfond Pharmaceutical Co., Zhumadian 463000, China; Laboratory of Cardio-cerebrovascular Drug, Henan Province, China. Electronic address: maliying@zzu.edu.cn.
  • 4 School of Basic Medical Science, Zhengzhou University, Zhengzhou 450001, China. Electronic address: saiyangz@zzu.edu.cn.
  • 5 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: zhaobing@zzu.edu.cn.
PMID: 36216031 DOI: 10.1016/j.bmcl.2022.129020
Abstract

In order to find high-efficiency and low-toxic anti-tumor drugs, 29 pyrido[3,4-d]pyrimidine compounds were designed, synthesized and evaluated by MTT assay in vitro. The results presented that most of the compounds had good antitumor activities, among which compound 30 had the best anti-tumor activity on MGC803 cells (IC50 = 0.59 μM). Mechanistic studies exhibited that compound 30 inhibited migration of MGC803 and induced Apoptosis. It was proved that compound 30 up-regulated expression of Bid and PARP, down-regulated expression of CycD1 by western blot experiments. This study indicated that compound 30 might be served as a lead agent for the treatment of human gastric cancers.

Keywords

Antitumor activity; Apoptosis; Proliferation; Pyrido[3,4-d]pyrimidine derivatives.

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