Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC50 range 15.8–26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC50 range 33.1–46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.
Many antibiotic substances have been isolated from algae, but little from marine green microalgae like Dunaliella salina. To examine the antibiotic effect of extracts from Dunaliella salina and Chlorella vulgaris, methanolic extracts were tested against Proteus vulgaris, Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhi ATCC 6534, E. coli ATCC 8739, S. aureus ATCC 25923 and B. subtilis ATCC 6635.Algae biomass were subjected to methanol/acetic acid treatments, dried and resuspended in methanol. The microorganisms were grown in a Mueller Hinton culture media; for the agar diffusion test were adjusted to tube 1 nephelometer and spread on plates; extracts were impregnated onto paper discs. After incubation inhibition zones around each disc were measured. One‐way ANOVA Dunnett analysis was performed.The D. salina extract showed significant antibacterial activity against all microorganisms, especially to Proteus vulgaris and Salmonella typhi ATCC 6534; while the C. vulgaris extract did not show significant antibacterial activity against all microorganisms, but the bigger inhibition halos result with B. subtilis and B. subtilis ATCC 6635.Support from SIP‐IPN and COFAA‐IPN.
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