title: Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents.
abstract: BACKGROUND
  Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design.
  
  
  METHODS
  Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain.
  
  
  RESULTS
  Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 µM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity.
  
  
  CONCLUSIONS
  Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound.
authors.forename: Silvia
authors.initials: S
authors.lastname: Elizondo-Jimenez
authors.forename: Antonio
authors.initials: A
authors.lastname: Moreno-Herrera
authors.forename: Rogelio
authors.initials: R
authors.lastname: Reyes-Olivares
authors.forename: Edith
authors.initials: E
authors.lastname: Dorantes-Gonzalez
authors.forename: Benjamín
authors.initials: B
authors.lastname: Nogueda-Torres
authors.forename: Eduardo A Gamosa de
authors.initials: EAG
authors.lastname: Oliveira
authors.forename: Nelilma C
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Lima
authors.forename: Isidro
authors.initials: I
authors.lastname: Palos
authors.affiliation: Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elias Pina, 88710, Reynosa, Mexico.
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
mesh_terms: D001554:Benzene / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006835:Hydrazones; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D001554:Benzene
keywords: Benzenesulfonyl; N-propionyl benzenesulfonylhydrazone; Trypanosoma cruzi; chagas disease; cruzain; inhibitors