2. Academic Validation
  3. Monodisperse oligoethylene glycols modified Camptothecin, 10-Hydroxycamptothecin and SN38 prodrugs

Monodisperse oligoethylene glycols modified Camptothecin, 10-Hydroxycamptothecin and SN38 prodrugs

  • Bioorg Med Chem Lett. 2019 Feb 15;29(4):581-584. doi: 10.1016/j.bmcl.2018.12.059.
Tao Deng 1,  Xianglan Mao 1,  Yan Xiao 2,  Zhigang Yang 1,  Xing Zheng 2,  Zhong-Xing Jiang 3
Affiliations

Affiliations

  • 1 Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
  • 2 Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China.
  • 3 Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China. Electronic address: zxjiang@whu.edu.cn.
PMID: 30600208 DOI: 10.1016/j.bmcl.2018.12.059
Abstract

Camptothecin, which represents a class of Natural Products with high Anticancer activity, suffers low water solubility which hampers its clinic application. To address this issue, monodisperse polyethylene glycols were employed to modify this class of Natural Products, including Camptothecin, 10-Hydroxycamptothecin, and SN38. Through selective modification with a series of monodisperse polyethylene glycols, 31 Camptothecin derivatives, including 9 ethers and 22 carbonates, were prepared using a macrocyclic sulfate-based strategy with high efficacy. Monodisperse polyethylene glycols modification provided the Camptothecin derivatives with high purity and fine-tunable water solubility. Through the physicochemical and biological assays, a few novel prodrugs with good solubility, cytotoxicity, and valuable drug release profile were identified as promising Anticancer drug candidates.

Keywords

Anticancer drugs; Camptophecin; Polyethylene glycols; Prodrug; SN38.

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