Novel Pyrazolo[3,4-d]pyrimidine Derivatives as Potential Antitumor Agents: Exploratory Synthesis, Preliminary Structure-Activity Relationships, and in Vitro Biological Evaluation

Molecules

Hai-Yun He¹  Jin-Ni Zhao¹  Ruo Jia¹  Ying-Lan Zhao¹  Sheng-Yong Yang¹  Luo-Ting Yu¹ 

[1] ¹State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicinal School, Sichuan University, Chengdu 610041, Sichuan, China ²College of Chemistry and Chemical Engineering, Chongqing University of Science and Technology, Chongqing 401331, China ^†These authors equally contributed to this work.

关键词: pyrazolo[3;    4-d]pyrimidine;    exploratory synthesis;    anticancer activity;    apoptosis;   

DOI  :  10.3390/molecules161210685

来源: mdpi

【 摘 要 】

In a cell-based screen of novel anticancer agents, the hit compound 1a which bears a pyrazolo[3,4-d]pyrimidine scaffold exhibited high inhibitory activity against a panel of four different types of tumor cell lines. In particular, the IC₅₀ for A549 cells was 2.24 µM, compared with an IC₅₀ of 9.20 µM for doxorubicin, the positive control. Four synthetic routes of the key intermediate 3 of 1a were explored and 1a was prepared via route D on the gram scale for further research. Two analogs of 1a were synthesized and their preliminary structure-activity relationships were studied. Flow cytometric analysis revealed that compound 1a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. These results suggest that the target compound 1a and its analogs with the pyrazolo[3,4-d]pyrimidine scaffold might potentially constitute a novel class of anticancer agents, which requires further studies.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.