Abstract

ARROYAVE, Jhonatan; BLAIR, Silvia  and  RESTREPO-SANCHEZ, Nora. DIOSGENONE-ARTESUNATE HYBRID HEMISYNTHESIS AND ITS ANTIMALARIAL EFFECT. Vitae [online]. 2014, vol.21, n.3, pp.211-217. ISSN 0121-4004.

Background: The malaria is a disease caused by parasites of genus Plasmodium and transmitted by mosquitoes of genus Anopheles. Annually about 220 million cases of malaria are reported worldwide, of which about 650000 people die, making this disease a public health problem worldwide. In the last years it has been reported drug resistance of parasite to antimalarials like chloroquine, mefloquine and recently, artemisinins derivatives like artesunato. Objective: Obtaining by hemisynthesis, a diosgenone-artesunate hybrid with a hydrolysable ester type linker, and evaluate its antiplasmodial activity and cytotoxicity in vitro. Methods: The carbonyl group of diosgenone was reduced in the presence of sodium borohydride to generate an alcohol, which was used as the binding moiety with artesunate, via an esterification reaction promoted by Yamaguchi's reagent. The antiplasmodial activity was determined in P. falciparum chloroquine-sensitive strains, while the cytotoxicity was evaluated in HepG2 cell line. Results: Through an esterification reaction with Yamaguchi reagent, it was obtained the first diosgenone-artesunate hybrid 4 (IC₅₀=0,0157 μM), which was more active than the native molecule, the diosgenone 1 (IC₅₀=35,49 μM) and the reduced diosgenone 2 (IC₅₀=46,33 μM), but it was not more active than the artesunate 3 (IC₅₀=0,0020 μM). Conclusions: A new diosgenone-artesunate hybrid was obtained, which presents better activity than the native molecule; result of importance for its potential use against artesunate resistant strains.

Keywords : Antimalarial hybrids; diosgenone; artesunate; malaria; Plasmodium.

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