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BIBTEX RIS

Novel dialkylphosphorylhydrazones: Synthesis, leishmanicidal evaluation and theoretical investigation of the proposed mechanism of action

2015; Elsevier BV; Volume: 101; Linguagem: Inglês

10.1016/j.ejmech.2015.06.014

1768-3254

Carolina Barbosa Brito da Matta, Aline Cavalcanti de Queiroz, Mariana da Silva Santos, Magna Suzana Alexandre‐Moreira, Vinícius Tomaz Gonçalves, Catarina de Nigris Del Cistia, Carlos Maurício R. Sant’Anna, João Batista Neves DaCosta,

Research on Leishmaniasis Studies

As part of a program to develop new drugs for the treatment of neglected diseases, new dialkylphosphorylhydrazones were synthesized and evaluated against the trypanosomatid parasites Leishmania braziliensis and Leishmania amazonensis. The synthesis of these compounds proved satisfactory with yields ranging from moderate to good. The most active compounds against L. braziliensis presented IC50 values in the 10−2 μM range, similar to that of the reference drug pentamidine. Two compounds, 4m and 4n, showed a significant dose dependent decrease in the infection index of L. amazonensis infected macrophages and caused a complete healing of nodules and ulcers when tested in vivo against L. amazonensis-infected mice, but the control of parasite burden at the inoculation site was statistically significant only in the case of treatment with 4n. A target fishing (reverse docking) approach using molecular docking with 15 enzymes of L. braziliensis indicated that the probable target of the active compounds was hexokinase, the first enzyme of the glycolytic pathway.