A series of camptothecin prodrugs exhibit HDAC inhibition activity. Issue 16 (1st September 2018)

• Record Type: Journal Article
• Authors: Zhu, Qiwen; Yu, Xumeng; Shen, Qianqian; Zhang, Qiumeng; Su, Mingbo; Zhou, Yubo; Li, Jia; Chen, Yi; Lu, Wei
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 16(2018)
• Page Start: 4706
• Page End: 4715
• Publication Date: 2018-09-01
• Subjects: Camptothecin -- HDAC -- SAHA -- Prodrug; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.08.008
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Camptothecin plays an important role in clinical cancer treatment, and its derivatives are a favorite of pharmaceutical chemists. Herein, we have designed a series of camptothecin prodrugs that exhibit histone deacetylase (HDAC) inhibition activity based on the synergy effect between HDAC inhibitors and camptothecin derivatives. With the evaluation of stability in buffers or plasma from human or mouse model, an appropriate linker was found, so the active drug can be released efficiently and compound 21a exhibited strong antiproliferative activity in A549 and HCT-116 cell lines. These results indicated that the well-designed prodrug can be promising in cancer treatment.