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

Author(s): 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.

Journal Name: Current Computer-Aided Drug Design

Volume 11 , Issue 1 , 2015

Become EABM
Become Reviewer


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.

Keywords: 3D-QSAR, 4D-QSAR, 5D-QSAR, mathematical regularization, nitrothiazole, PFOR, QSAR pitfalls, tizoxanide.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2015
Page: [21 - 31]
Pages: 11
DOI: 10.2174/1573409911666150414145937

Article Metrics

PDF: 71
PRC: 2