Design, synthesis and biological evaluation of 2, 3-dihydroimidazo[1, 2-c]quinazoline derivatives as novel phosphatidylinositol 3-kinase and histone deacetylase dual inhibitors. Issue 82 (10th November 2017)

• Record Type: Journal Article
• Authors: Wu, Yichao; Dai, Weichen; Chen, Xin; Geng, Aixin; Chen, Yadong; Lu, Tao; Zhu, Yong
• Is Part Of: RSC advances. Volume 7:Issue 82(2017)
• Page Start: 52180
• Page End: 52186
• Publication Date: 2017-11-10
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra08835c
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A novel design approach by combination of PI3K and HDAC inhibitory activity in one molecule to produce dual inhibitors. Abstract : Histone deacetylase (HDAC) inhibitors are known to induce multiple epigenetic modifications affecting signaling networks and act synergistically with phosphatidylinositol 3-kinase (PI3K) inhibitors for the treatment of cancer. Herein we present a novel design approach for cancer drug development by incorporating HDAC inhibitory functionality into a PI3K inhibitor pharmacophore to construct dual-acting inhibitors. The designed compounds were synthesized and showed inhibitory activities against PI3K and HDAC. The representative dual PI3K/HDAC inhibitors, compounds12a–j, showed potent antiproliferative activities against K562 and Hut78 in cellular assays. This work may lay the foundation for developing novel dual PI3K/HDAC inhibitors as potential anticancer therapeutics.