期刊
ACS OMEGA
卷 5, 期 46, 页码 29733-29745出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.0c03505
关键词
-
资金
- Thailand Research Fund [RSA5880007]
- Royal Golden Jubilee Ph.D. (RGJ-Ph.D.) Program [PHD/0198/2556, PHD/0052/2557]
- Faculty of Medicine Research Fund, Chiang Mai University [045/2561, 095/2561]
- Robert A. Welch Foundation [E-1320]
Perylene diimide (PDI) derivatives have been studied as G-quadruplex ligands that suppress telomerase activity by facilitating G-quadruplex formation of telomeric DNA and the hTERT promoter. PIPER, the prototypical PDI, reduces telomerase activity in lung and prostate cancer cells, leading to telomere shortening and cellular senescence of these cells. However, PIPER suffers from poor hydrosolubility and the propensity to aggregate at neutral pH. In this report, we synthesized a new asymmetric PDI, aPDI-PHis, which maintains one N-ethyl piperidine side chain of PIPER and has histidine as another side chain. The results show that aPDI-PHis is superior to its symmetric counterparts, PIPER and PDI-His, in terms of hydrosolubility, G-quadruplex binding, cellular uptake, and telomerase inhibition in prostate cancer cells. These results suggest that one N-ethyl piperidine side chain of PDI is sufficient for G-quadruplex binding, while another side chain can be tuned to elicit desirable properties. These findings might lead to better PDIs for use as anticancer drugs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据