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

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

Volume: 11 Issue: 1

Author(s): Thomas Scior, Jorge Lozano-Aponte, Subhash Ajmani, Eduardo Hernández-Montero, Fabiola Chávez-Silva, Emanuel Hernández-Núñez, Rosa Moo-Puc, Andres Fraguela-Collar and Gabriel Navarrete-Vázquez

Affiliation:

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

Abstract: 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.

Cite this article as:

Scior Thomas, Lozano-Aponte Jorge, Ajmani Subhash, Hernández-Montero Eduardo, Chávez-Silva Fabiola, Hernández-Núñez Emanuel, Moo-Puc Rosa, Fraguela-Collar Andres and Navarrete-Vázquez Gabriel, Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight, Current Computer-Aided Drug Design 2015; 11 (1) . https://dx.doi.org/10.2174/1573409911666150414145937