61922-09-6Relevant articles and documents
Novel dialkylphosphorylhydrazones: Synthesis, leishmanicidal evaluation and theoretical investigation of the proposed mechanism of action
Da Matta, Carolina Barbosa Brito,De Queiroz, Aline Cavalcanti,Santos, Mariana Silva,Alexandre-Moreira, Magna Suzana,Gon?alves, Vinicius Tomaz,Del Cistia, Catarina De Nigris,Sant'Anna, Carlos Mauricio R.,DaCosta, Jo?o Batista N.
, p. 1 - 12 (2015/06/30)
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.
Diastereoselective synthesis of new dialkylphosphorylhydrazones
Rodrigues, Janaina Marques,Sant'anna, Carlos Mauricio R.,Rumjanek, Victor Marcos,Dacosta, Joao Batista Neves
experimental part, p. 40 - 56 (2010/04/26)
A series of 22 dialkylphosphorylydrazones (dialkyl ester, N′-[(1E)-(R1 phenyl)methylene]-phosphorohydrazidic acid), 20 of them new, along with three new N,N′-bis (diisobutylphosphorylthioamide)diamines (bis-[diisobutyl ester), N-thioxomethylene]-, diamine)phosphora-midic acid, were prepared and characterized by IR, 1H NMR, 13C NMR, 31P NMR, and mass spectrometry. The analysis of 1H NMR, 13C NMR, 31P NMR, and NOE spectra confirmed the observation of the single diastereoisomer E in the synthesis of dialkylphosphorylydrazones. The results of a molecular modeling study performed in order to investigate the mechanism of the synthesis of dialkylphosphorylydrazones are in agreement with the experimental results, i.e., the favored formation of diastereoisomer E over Z.
