title: Studies on 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole/2-hydroxypropyl-β-cyclodextrin association: Characterization, molecular modeling studies, and in vivo anthelminthic activity.
abstract: The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability constant and stoichiometric ratio determined by phase-solubility diagram and Job's plot provided evidence that HPβCD enhanced water solubility of RCB20 through inclusion complex formation. Two-dimensional ¹H NMR spectroscopy is used to study the molecular arrangement of inclusion complex in solution. These results are further supported using molecular modeling studies. In the solid state, the complexation is confirmed by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy. Finally, RCB20/HPβCD complex has better activity than RCB20 against the adult and muscle larvae phase of Trichinella spiralis.
authors.affiliation: Departamento de Farmacia, UNAM, México DF, Mexico.
authors.forename: Yareli
authors.initials: Y
authors.lastname: Rojas-Aguirre
authors.forename: Lilián
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: Ivan
authors.initials: I
authors.lastname: Castillo
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Olivia
authors.initials: O
authors.lastname: Soria-Arteche
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D014235:Trichinellosis / Q000188:drug therapy; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: C557917:6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole; D000871:Anthelmintics; D001562:Benzimidazoles; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin