Novel quinazolin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity |
| |
Affiliation: | 1. Eurofins Advinus Limited, Bengaluru 560058, India;2. Vellore Institute of Technology, Vellore 632014, India |
| |
Abstract: | We report the design, synthesis and biological evaluation of 17 novel 8-aryl-2-morpholino-3,4-dihydroquinazoline derivatives based on the standard model of DNA-PK and PI3K inhibitors. Novel compounds are sub-divided into two series where the second series of five derivatives was designed to have a better solubility profile over the first one. A combination of in vitro and in silico techniques suggested a plausible synergistic effect with doxorubicin of the most potent compound 14d on cell proliferation via DNA-PK and poly(ADP-ribose) polymerase-1 (PARP-1) inhibition, while alone having a negligible effect on cell proliferation. |
| |
Keywords: | DNA-dependent protein kinase Poly(ADP-ribose) polymerase-1 Phosphatidylinositol 3-kinase NU7441 Cancer Chemosensitization ATM" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" ataxia telangiectasia mutated ATR" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" ataxia telangiectasia and Rad3-related DCM" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" dichloromethane DDR" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" DNA-damage response DNA-PK" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" DNA-dependent protein kinase DOX" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" doxorubicin DSB" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" double strand break GP" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" growth percentage IR" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" ionizing radiation NHEJ" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" non-homologous end joining MTD" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" maximum tolerated dose PARP-1" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" poly(ADP-ribose) polymerase-1 PI3K" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol 3-kinase PIKK" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol 3-kinase related protein kinase SSB" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" single-strand break THF" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" tetrahydrofuran Xphos" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl |
本文献已被 ScienceDirect 等数据库收录! |
|