Design, Synthesis and Biological Evaluation of Novel (Quinolinyl-3-pyridinyl)benzenesulfonamide-Based Hydroxamic Acids as PI3K and HDAC Dual Targeting Inhibitors

Abstract

Polypharmacology has emerged as a promising approach to drug discovery, especially antitumor drug. This study reports the design, synthesis, and biological evaluation of novel phosphatidylinositol 3-kinases (PI3Ks) and histone deacetylases (HDACs) dual inhibitors on the basis of GSK2126458 under clinical evaluation and vorinostat approved. Among these hybrid molecules, GYB-4 and GYB-5 possessed potent inhibition against both PI3Kα (1.0 and 1.3 nmol/L, respectively) and HDAC1 (4.2 and 4.8 nmol/L, respectively). Antiproliferative assays with HCT116, PC3 and A2780 cell lines subsequently were performed. The structure-activity relationship study will guide to optimization of dual PI3K and HDAC inhibitors.

Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives

“…Quinolines, as one class of N -containing heterocycles, have numerous advantages over other non-nitrogenous, which are widely used as “parental” compounds to synthesize molecules with variety of promising biological activity [ 16 , 17 , 18 , 19 ]. The quinoline motifs are frequently found in many compounds that show potent anticancer activity with different mechanisms [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Anlotinib [ 23 ] (multi-kinase inhibitor) and Bosutinib [ 24 ] (Src-Abl inhibitor), which are quinoline-based protein kinase inhibitors, have been approved for the treatment of human cancers.…”