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Bioassay-guided screening of Hypoestes verticillaris whole plant CH2Cl2: MeOH (1:1) extract for anti-plasmodial activity yielded four new compounds: two lignans 2, 6-dimethoxysavinin (1), 2,6-dimethoxy-(7E)-7,8-dehydroheliobuphthalmin (2); and two fusicoccane diterpenoids: 11(12)-epoxyhypoestenone (3) and 3(11)-epoxyhypoestenone (4). The chemical structures were determined using various spectroscopic techniques: UV-vis, IR, CD, 1D, 2D and MS. Two fractions (RAO-43B and RAO-43D) and the isolated compounds were tested for activity against CQ susceptible (D6) and resistant (W2) Plasmodium falciparum parasite strains, in vitro and the IC50 values determined. While the whole extract and some resultant fractions displayed moderate activity, the isolated compounds exhibited mild anti-plasmodial activity against the both strains ranging from IC50 value of 328 mu M in 1 to 93 mu M in 3 against W2 strain.