Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight

نویسندگان

  • Thomas Scior
  • Jorge Lozano-Aponte
  • Subhash Ajmani
  • Eduardo Hernández-Montero
  • Fabiola Chávez-Silva
  • Emanuel Hernández-Núñez
  • Rosa Moo-Puc
  • Andres Fraguela-Collar
  • Gabriel Navarrete-Vázquez
چکیده

In view of the serious health problems concerning infectious diseases in heavily populated areas, we followed the strategy of lead compound diversification to evaluate the near-by chemical space for new organic compounds. To this end, twenty derivatives of nitazoxanide (NTZ) were synthesized and tested for activity against Entamoeba histolytica parasites. To ensure drug-likeliness and activity relatedness of the new compounds, the synthetic work was assisted by a quantitative structure-activity relationships study (QSAR). Many of the inherent downsides - well-known to QSAR practitioners - we circumvented thanks to workarounds which we proposed in prior QSAR publication. To gain further mechanistic insight on a molecular level, ligand-enzyme docking simulations were carried out since NTZ is known to inhibit the protozoal pyruvate ferredoxin oxidoreductase (PFOR) enzyme as its biomolecular target.

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عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2015