AUTHOR=Yang Chao , Xia An-Jie , Du Cheng-Hao , Hu Ming-Xing , Gong You-Ling , Tian Rong , Jiang Xin , Xie Yong-Mei 

TITLE=Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1014854

DOI=10.3389/fphar.2022.1014854

ISSN=1663-9812

ABSTRACT=<p>7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan <italic>in vitro</italic>. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake <italic>via</italic> glucose transporters, which are overexpressed in most cancers. The <italic>in vitro</italic> antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named <bold>5b</bold> showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, <bold>5b</bold> remarkably inhibited the growth of HCT116 <italic>in vivo</italic>. These results suggested that <bold>5b</bold> could be a promising drug candidate for treating colorectal cancer.</p>