Romanian Society of Pharmaceutical Sciences

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

HEGIRA RAMÍREZ 1,2, JOSÉ DOMÍNGUEZ 1, ESTEBAN FERNANDEZ-MOREIRA 3, JUAN RODRIGUES 4, MIGUEL RODRÍGUEZ 1, JAIME E. CHARRIS 1*

1Organic Synthesis Laboratory, Faculty of Pharmacy, Central University of Venezuela, 47206, Los Chaguaramos 1041-A, Caracas, Venezuela
2Facultad de Medicina, Universidad de Las Américas, Quito, Ecuador
3Escuela de Medicina, Universidad Espíritu Santo, Samborondón, Ecuador
4Departamento de Tecnología de Procesos Biológicos y Bioquímicos, División de Ciencias Biológicas, Universidad Simón
Bolívar, Valle de Sartenejas, 9063971, Caracas, Venezuela

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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 hemindependent 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.