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Cyclooxygenase (COX) is the key enzyme responsible for the production of prostanoids. It plays important roles in the inflammatory process and pathogenesis of several diseases, including malaria. However, there has been no information of the inhibitory effects of COX inhibitors on inflammatory mediators and standard antimalarial drugs. Therefore, in this study, both selective and non-selective COX-2 inhibitors (aspirin, ibuprofen, piroxicam, and naproxen), alone or in combination, were investigated for their antimalarial activities in vitro. The antimalarial activity was assessed using the SYBR Green I fluorescent-based technique. For mefloquine- aspirin combination, the test wells consisted of mefloquine and aspirin at the ratios of 200:0, 140:30000, 100:50000, 60:70000, and 0:100000 nM. The concentration ratios for artesunate-aspirin were 50:0, 35:30000, 25:50000, 15:70000, and 0:100000 nM. The median (range) concentrations that inhibited parasite growth by 50% (IC50) of aspirin for K1 and 3D7 clones were 1,889 (1,600-2,792) and 2,417 (912-2,630) nM, respectively. The corresponding values of mefloquine were 10.1 (8.1-13.9) and 23.4 (22.9-24.7) nM, respectively. The corresponding values of artesunate were 2.5 (1.6-3.4) vs. 2.2 (1.2-3.2) nM, respectively. The corresponding values for mefloquine were 10 (8-14) and 23 (23-25) nM, respectively. The corresponding values for artesunate were 2.5 (2-3) vs. 2 (1-3) nM, respectively. The IC50 values of ibuprofen, piroxicam and naproxen were higher than 100,000 nM for both clones. The median (range) sum fractional inhibitory concentrations (FIC) of mefloquine-aspirin interaction for K1 and 3D7 P. falciparum clones were 0.82 (0.79-1.0) and 0.97 (0.83-1.1), respectively. The corresponding sum FICs of artesunate-aspirin were 0.94 (0.88-0.95) and 0.95 (0.92-0.97), respectively. Results indicate indifferent antimalarial interaction between these two drugs when used in combination.
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