title: Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight.
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.
authors: Department of Pharmacy, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Edificio 105 C/106, C.P. 72570 Puebla, PUE., Mexico. tscior@gmail.com.
authors: Thomas
authors: T
authors: Scior
authors: Jorge
authors: J
authors: Lozano-Aponte
authors: Subhash
authors: S
authors: Ajmani
authors: Eduardo
authors: E
authors: Hernández-Montero
authors: Fabiola
authors: F
authors: Chávez-Silva
authors: Emanuel
authors: E
authors: Hernández-Núñez
authors: Rosa
authors: R
authors: Moo-Puc
authors: Andres
authors: A
authors: Fraguela-Collar
authors: Gabriel
authors: G
authors: Navarrete-Vázquez
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000201:enzymology*; D004749:Entamoebiasis / Q000188:drug therapy / Q000469:parasitology; D006801:Humans; D062105:Molecular Docking Simulation; D009574:Nitro Compounds; D050743:Pyruvate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D009574:Nitro Compounds; D013844:Thiazoles; D050743:Pyruvate Synthase; C041747:nitazoxanide