Development of pyrazolo[3,4-d]pyrimidin-4-one scaffold as novel CDK2 inhibitors: Design, synthesis, and biological evaluation
| Autor: | Fan Xie, Liying Zhou, Changwei Ge, Xiuqing Song, Hong Yan |
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| Rok vydání: | 2022 |
| Předmět: |
Dose-Response Relationship
Drug Molecular Structure Organic Chemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Structure-Activity Relationship Cell Line Tumor Drug Design Drug Discovery Molecular Medicine Pyrazoles Drug Screening Assays Antitumor Molecular Biology Protein Kinase Inhibitors Cell Proliferation Etoposide |
| Zdroj: | Bioorganicmedicinal chemistry letters. 70 |
| ISSN: | 1464-3405 |
| Popis: | A series of pyrazolo[3,4-d]pyrimidin-4-one scaffold were designed and synthesized as novel CDK2 inhibitors. By analyzing the common motifs of various known inhibitors, the designed compounds 1 were virtually screen for their inhibitory activity by docking into the active pocket of CDK2. The influence of different substitutes on the docking results was investigated. A total of 15 pyrazolo[3,4-d]pyrimidin-4-ones 1 were synthesized by Paal-Knorr reaction, pyrimidine ring closure, bromination, Suzuki coupling reaction, amide formation and Knoevenagel condensation. The Cell Counting Kit-8 (CCK-8) was used to evaluate the inhibitory activity of pyrazolo[3,4-d]pyrimidin-4-ones 1 in the breast cancer cell line MCF-7 in vitro using Etoposide as a reference control substance. The screening results demonstrated that the designed compounds have significant antiproliferative activity, and compounds 1e and 1j were the most active compounds with IC |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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