Design, in-silico ADME Study and molecular docking study of novel quinoline-4-on derivatives as Factor Xa Inhibitor as Potential anti-coagulating agents

Abstract

The main aim of present work is to identification of potency of novel quinoline-4-one derivatives as a factor Xa inhibitors by in-silico ADME study and molecular docking study. Factor Xa is enzyme which play major role in blood coagulation process by conversation of prothrombine to thrombine. Thrombine is the protein which converts fibrinogen to fibrin (clot). Inhbition of factor Xa is altimetly inhbition of blood coagulation process. Due to the abnormal blood coagulation, serious to very serious problems can create and will lead to death. Betrixaban, Rivaroxaban, Epixaban and Edoxaban which are FDA approval dugs as factor Xa inhibitors. They are very potent drugs and very few side effects compare to other available anti-coagulating drugs so they was taken as a reference molecules for current study. Some novel quinoline-4-one derivatives was design and screened for factor Xa enzyme. We design 26 compounds and first they screen for in-silico ADME parameters. Very few compounds not pass Lipinski rule. A majority compound shows excellent in-silico ADME properties. In molecular docking study almost all compound shows near binding energy to reference drug and shows almost near dock score. Q23 and Q26 show excellent inhibitory activity against Factor Xa. 13 molecules shows very near dock score compare to reference drugs. This study became a reference and provides valuable data for the synthesis, in-vitro and in-vivo evaluation of quinolone-4-on derivatives as Factor Xa inhibitors.