发现高效且选择性的7-乙基-10-羟基喜树碱-葡萄糖缀合物作为潜在的抗结直肠癌药物。
Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents.
作者信息
Yang Chao, Xia An-Jie, Du Cheng-Hao, Hu Ming-Xing, Gong You-Ling, Tian Rong, Jiang Xin, Xie Yong-Mei
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.
Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University Medical College, Shenzhen, Guangdong, China.
出版信息
Front Pharmacol. 2022 Nov 23;13:1014854. doi: 10.3389/fphar.2022.1014854. eCollection 2022.
7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100-1000 folds more than irinotecan . 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 glucose transporters, which are overexpressed in most cancers. The antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, remarkably inhibited the growth of HCT116 . These results suggested that could be a promising drug candidate for treating colorectal cancer.
7-乙基-10-羟基喜树碱（SN38）是伊立替康的一种高效代谢产物，其抗癌功效比伊立替康高100至1000倍。然而，由于治疗窗口非常窄且水溶性差，SN38的临床应用受到限制。在此，我们报道了SN38-葡萄糖缀合物（Glu-SN38），由于其能选择性摄取在大多数癌症中过度表达的葡萄糖转运蛋白，从而能够靶向癌细胞。研究了Glu-SN38对人癌细胞系和正常细胞的抗增殖活性。其中一种名为的缀合物对人结肠癌细胞系HCT116显示出高效力和选择性。此外，显著抑制了HCT116的生长。这些结果表明，可能是一种有前途的治疗结肠癌的候选药物。
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