2. Academic Validation
  3. Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment

Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment

  • Bioorg Med Chem Lett. 2023 Feb 1:81:129128. doi: 10.1016/j.bmcl.2023.129128.
Ruiming Zhang 1,  Yi Luo 2,  Chenghao Du 3,  Ling Wu 1,  Yankang Wang 1,  Yuanduan Chen 4,  Shouqian Li 4,  Xin Jiang 5,  Yongmei Xie 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China.
  • 2 Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • 3 Department of Biological Sciences, USC Dana and David Dornsife College of Letters, Arts and Sciences, Los Angeles 90089, USA.
  • 4 Guizhou Jinqianguo Biotechnology Co. Ltd., Bijie 551714, PR China.
  • 5 Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: jiangxin1975@126.com.
  • 6 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China. Electronic address: xieym@scu.edu.cn.
PMID: 36639036 DOI: 10.1016/j.bmcl.2023.129128
Abstract

7-Ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of irinotecan (CPT-11), has been shown to be 100-1000 times more effective than CPT-11. However, the poor water solubility and bioavailability of SN38 constrained its clinical application. In this study, we synthesized a novel SN38-glucose conjugate (FSY04) to address this issue. Our in vitro studies indicated that FSY04 had a potent inhibitory ability against colorectal Cancer (CRC) cell lines of SW-480 and HCT-116 compared to the inhibitory capacity of CPT-11. Interestingly, FSY04 possessed lower cytotoxicity against normal cell lines of LO2 and 293T in contrast with CPT-11. Moreover, FSY04 is more active than CPT-11 in inducing Apoptosis, inhibiting migration, and invasion. In vivo experiments suggested that half of the equivalent of FSY04 inhibited the growth of SW480 in the xenograft tumor model better than one equivalent of CPT-11. Our data demonstrated FSY04 to be a promising agent in CRC therapy.

Keywords

7-Ethyl-10-hydroxycamptothecin; Antitumor activity; Camptothecin; Colorectal cancer; Prodrug.

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