Molecular Docking and Molecular Dynamics Simulation Studies of Quinoline-3-Carboxamide Derivatives with DDR Kinases–Selectivity Studies towards ATM Kinase

Quinoline-3-carboxamides are an essential class of drug-like small molecules that known to inhibit the phosphatidylinositol 3-kinase-related kinases (PIKK) family kinases. The quinoline nitrogen is shown bind hinge region kinases, making them competitive inhibitors adenosine triphosphate (ATP). We have previously designed and synthesized quinoline-3-carboxamides as potential ataxia telangiectasia mutated (ATM) kinase function adjuvant treatment with DNA damaging agents. This article discusses molecular docking studies performed these derivatives damage response (DDR) kinases-ATM, rad3 related (ATR), dependent protein catalytic subunit (DNA-PKcs) highlights their selectivity towards ATM kinase. Docking were also mTOR PI3Kγ, which close homologs DDR Molecular dynamics simulations for one against all enzymes establish stability interactions involved. Finally, absorption, distribution, metabolism, excretion (ADME) properties predicted using QikProp manual in Maestro. In conclusion, showed high comparison other though sequence similarity between was relatively high.