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Antimalarial plantGuiera senegalensis ("Senegal guiera" in English; "Sabara" in Hausa) (Combretaceae) is used for the management of malaria in Africa and other parts of the world with little or no scientific backing on its active component(s). Thus, the aim of this research was to characterize compounds from Guiera senegalensis(GS) ethylacetate extract in an attempt to provide an insight for the identification of lead molecules for drugs development. The study assayed for in vitro antiplasmodial activity of different extracts (n-hexane, chloroform, ethylacetate and methanol) of the plant. The most active extract wasfractionated using column chromatography. Further fractionation and isolation (Preparatory Thin Layer Chromatography) were guided by in vitro antiplasmodial assay and the characterization/identification of compounds done by LC/MS (QTOF-MS/MS in positive and negative ion modes) and supported by FTIR. The ethylacetate extractwas found to have bestantimalarial activity over the remaining solvent extracts tested (hexane, chloroform, and methanol extracts) and therefore chosen for the study. Fractionation of this ethylacetate extract gave eight (8) fractions and in vitro antiplasmodial assay on the fractions revealed GS-8 fraction to have the best % inhibition in parasitaemia. Preparatory-TLC with hexane:ethyleacetate:methanol (3:2:2) revealed 7 compounds. In vitro antiplasmodial activity showed sub-fraction GS-8B to have the highest percentage inhibition. Thin layer chromatogram of GS-8B revealed two eluting compounds. The LC-MS (Q-TOF/MS-MS) in the positive and negative ion modes coupled with FTIR revealed that GS-8B compounds are mostly terpenoids and alkaloids. Labdene-13,14,15-triol, Quinoline, Labdane, Quinoxaline, Delta-Valerolactone and Ergostanol were isolated. In conclusion, the constituents of G. senegalensis ethylacetate leaf extract (especially the terpenoids and alkaloids) couldbe of great potential for anti-malarial drug developmentand beneficial in the management of malaria as used traditionally. [ABSTRACT FROM AUTHOR]