Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor.

Yongliang Li, Yuanpeng Liu, Yiran Chen, Kewei Wang, Yepeng Luan

Bioorganic & medicinal chemistry letters 2022 Sep 15

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Gemcitabine, as a first-line antitumor drug, has attracted extensive attention. However the occurrence of drug resistance limits its clinical utilization. In this paper, a gemcitabine prodrug GZ was designed and synthesized by conjugation of gemcitabine with a newly reported HDAC6 selective inhibitor pentadecanoic acid. GZ displayed high cytotoxicity to nine cancer cell lines with IC50 values in the low micromolar range. In vivo, GZ displayed superior antitumor activity to gemcitabine in a 4T1 tumor xenograft model without obvious pathological damage to important organs of mice. Our study showed that compound GZ is a potential gemcitabine prodrug, which is worthy of further antitumor activity exploration. Copyright © 2022. Published by Elsevier Ltd.

Citation

Yongliang Li, Yuanpeng Liu, Yiran Chen, Kewei Wang, Yepeng Luan. Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor. Bioorganic & medicinal chemistry letters. 2022 Sep 15;72:128881