Monodisperse oligoethylene glycols modified Camptothecin, 10-Hydroxycamptothecin and SN38 prodrugs. Issue 4 (15th February 2019)

• Record Type: Journal Article
• Authors: Deng, Tao; Mao, Xianglan; Xiao, Yan; Yang, Zhigang; Zheng, Xing; Jiang, Zhong-Xing
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 4(2019)
• Page Start: 581
• Page End: 584
• Publication Date: 2019-02-15
• Subjects: Camptophecin -- Prodrug -- Polyethylene glycols -- Anticancer drugs -- SN38; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.12.059
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Monodisperse oligoethylene glycol was employed to fine-tuning the water solubility and anticancer efficacy of Camptothecin, 10-Hydroxycamptothecin and SN38. 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.