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Universidad de Cartagena. Cartagena de Indias, Colombia. Nine quinone derivatives, three 2-hydroxy-1,4-naphthoquinone; three 4,5 and three 4,9-naphtho- quinone scaffolds, were synthesized and evaluated against 3D7 and Dd2 Plasmodium falciparum strains. Quinoid compounds showed half-maximal inhibitory concentration IC50 values in the micromolar range, and moderate toxicity against a human fibroblast cell line.
Additionally, the compounds produced morphological changes in the digestive vacuole of treated parasites, similar to those caused by protease inhibitors that block hemoglobin degradation pathway, which is essential for parasite development. Taken together, our results suggest that blocking of hemoglobin degradation pathway by inhibiting the cysteine peptidases present in the digestive vac- uole, could represent one of the mechanisms used by these compounds to antagonize the growth of malaria para- sites.
Nueve derivados de quinona tres 2-hidroxil-1,4-naftoquinonas, tres 4,5- y tres 4,9- naftoquinonas , se sintetizaron y evaluaron contra cepas 3D7 y Dd2 de Plasmodium falciparum. Despite live at continuous risk of infection 2. Due to the decades of sustained efforts, it remains a major lack of an effective vaccine 3, chemotherapy public health problem in Africa, South America constitutes the only line of defense against KEY WORDS: Antimalarial agents, Falcipain 2 inhibition, Plasmodium falciparum, Quinoid derivatives.
E-mail: rigaitan yahoo. Louis, MO, mechanisms of action The fluorogenic substrate for cysteine Hemoglobin degradation occurs within the proteases benzyloxycarbonyl-Leucyl-Arginyl digestive vacuole, an acidic and specialized or- aminomethyl coumarin Z-LR-AMC was ob- ganelle, where the globin component is degrad- tained from Bachem Bioscience Bubendorf, ed to small peptides by a complex combination Switzerland. All fine chemicals, solvents and of four aspartic plasmepsins: Plms , three cys- media components were obtained from Sigma- teine falcipains: FPs and one metallo fal- Aldrich.
Recently, the group of natural products of The privileged position of quinones in the University of Cartagena Colombia obtained medicinal chemistry derives from their chemical by chemical synthesis three series of quinone and structural properties Quinones are both derivatives: a lapachol analogues 3-alkenyl oxidants and potent electrophiles.