4,5-Dihydropyrazole derivatives containing oxygen-bearing heterocycles as potential telomerase inhibitors with anticancer activity
Telomere and telomerase were closely related to the occurrence and development of some cancers After the key active site of telomerase was identified,to enhance the ability of dihydropyrazole derivatives to inhibit telomerase,we designed a series of novel 4,5-dihydropyrazole derivatives containing heterocyclic oxygen moiety based on previous studies The telomerase inhibition assay showed that compound 10a displayed the most potent inhibitory activity with an IC50 value of 0.6 μM for telomerase.The antiproliferative assay showed that 10a exhibited high activity against human gastric cancer cell SGC-7901 with an ICso value of 10.95 ± 0.60 μM.Flow cytometric analysis and western blot results showed that 10a induced both apoptosis and autophagy.A docking simulation showed that 10a could bind well to the active site of telomerase and act as a telomerase inhibitor.The 3D-QSAR model was also built to provide a more pharmacological understanding that could be used to design new agents with more potent telomerase inhibitory activity.
Yin Luo Yang Zhou Jie Fu Hai-Liang Zhu
Staw Key Laboratory of Pltarniaceutical Biotechnology,Sanjing University,Nanjing,210093,People”s Rep Environmental Engineering Program,tJepartmeni of Civil Engineering,Auhstrn University,Auburn,AL,3683
国内会议
大连
英文
10-19
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）