Group of tropical and subtropical diseases caused by parasites and infectious agents is called neglected tropical diseases (NTDs). NTDs are prevalent in 149 countries; more than one billion people are affected with 534,000 deaths every year. Among NTDs we can cite Chagas diseases and Leishmaniasis, they have a high global rate of mortality and morbidity. Despite this fact, these diseases haven’t much attention from pharmaceutical companies. In this context, biochemical pathways important to the survival of the parasite have aroused interest in the study of new drugs. Cysteine proteases are prevalent in parasites and responsible for differentiation, immune evasion, for these reason should be used as target in drug design. Thereby, in this work we constructed a CPB2.8 model by comparative modeling technique. This model was refined by 100ns of Molecular Dynamic Simulation (MD) and stabilization was about 80ns. The molecular interaction fields (MIFs) were calculated in GRID program to suggest physicochemical properties of cysteine proteases cruzain from Trypanosoma cruzi (Chagas Disease) and CPB2.8 of Leishmania mexicana (Leishmaniasis). After these studies were proposed a pharmacophore model based on active site of these enzymes and favorable MIFs using SBDD tecniques that were validated by ROC curve in order to obtain a new inhibitor against these neglected diseases by virtual screening studies.

Molecular dynamic simulation and pharmacophore model of parasitic cysteine proteases

253rd National Meeting (2017)

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