Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC₅₀) of plant extracts ranged from 1.90 to >100 μg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC₅₀3D7/INDO = 4.91/6.64 μg/mL, 5.49/5.98 μg/mL, and 6.49/7.10 μg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC₅₀3D7/INDO = 6.41/8.10 μg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC₅₀3D7/INDO = 2.49/1.90 μg/mL and 3.70/2.80 μg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 μg/mL, giving selectivity indices (SIs) in the range of >31.20⁻80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria.

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