Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities

Zixue Zhang, Qingwei Zhang*, Hao Zhang, Minru Jiao, Zheng Guo, Xinyan Peng, Lei Fu, Jianqi Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo.

Original languageEnglish
Article number105407
JournalBioorganic Chemistry
Publication statusPublished - Dec 2021


  • Anti-proliferative activity
  • Histone deacetylases
  • Quinazolinyl
  • Selectivity
  • Tumor growth inhibition

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