咖啡因类似物对G2期检查点抑制的构效关系。
Structure-activity relationships for G2 checkpoint inhibition by caffeine analogs.
作者信息
Jiang X, Lim L Y, Daly J W, Li A H, Jacobson K A, Roberge M
机构信息
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
出版信息
Int J Oncol. 2000 May;16(5):971-8. doi: 10.3892/ijo.16.5.971.
Caffeine inhibits the G2 checkpoint activated by DNA damage and enhances the toxicity of DNA-damaging agents towards p53-defective cancer cells. The relationship between structure and G2 checkpoint inhibition was determined for 56 caffeine analogs. Replacement of the methyl group at position 3 or 7 resulted in loss of activity, while replacement at position 1 by ethyl or propyl increased activity slightly. 8-Substituted caffeines retained activity, but were relatively insoluble. The structure-activity profile did not resemble those for other known pharmacological activities of caffeine. The active analogs also potentiated the killing of p53-defective cells by ionizing radiation, but none was as effective as caffeine.
咖啡因可抑制由DNA损伤激活的G2检查点，并增强DNA损伤剂对p53缺陷癌细胞的毒性。对56种咖啡因类似物测定了其结构与G2检查点抑制之间的关系。3位或7位甲基的取代导致活性丧失，而1位被乙基或丙基取代则使活性略有增加。8位取代的咖啡因保留了活性，但相对不溶。构效关系图谱与咖啡因其他已知药理活性的图谱不同。活性类似物还增强了电离辐射对p53缺陷细胞的杀伤作用，但没有一种与咖啡因一样有效。
Zotero 插件