In this study, structure-activity relationship (SAR) guided design of eight series of the novel scaffold of chalcone by extensive SAR survey of active quinolinyl chalcones and prenylated chalcones from the literature, molecular hybridization of the pharmacophoric fragments resulted to 169 novel prenylated-quinolinyl chalcone hybrids. Molecular docking and pharmacokinetics studies were also conducted. We have previously report the synthesis and antimalarial of prenylated acetophenone fragment 8 .