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SYNTHESIS OF 4-BENZYLSULFANYL AND 4-BENZYLSULFONYL CHALCONES. BIOLOGICAL EVALUATION AS ANTIMALARIAL AGENTS

Abstract:

Malaria management has been complicated in recent times, perhaps, by increasing the Plasmodium spp. resistance to the drugs of clinical use for its treatment. The study describes the synthesis of a new series of chalcones 7-40 and their antimalarial efficacy against a chloroquine-susceptible strain of Plasmodium berghei. Furthermore, we carried out hemin-dependent studies to unfold the mechanism of action of these synthesized hybrid molecules. Twenty compounds showed inhibitory activity on the formation of β-hematin higher than 75%, compared to chloroquine. The compounds 9, 21, 33 and 37 showed enhanced antimalarial activity in vivo and may reduce malaria progression in this model through a mechanism related to the inhibition of hemozoin formation. Critical aspects of the structure-activity relationship (SAR) are also discussed to better understand the effect shown by these compounds.