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-VázquezPages 21-31 (11)
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.
Keywords:
3D-QSAR, 4D-QSAR, 5D-QSAR, mathematical regularization, nitrothiazole, PFOR, QSAR pitfalls, tizoxanide.
Affiliation:
Department of Pharmacy, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Edificio 105 C/106, C.P. 72570 Puebla, PUE., Mexico
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