TY - JOUR
T1 - Diversity in the supramolecular interactions of 5,6-dichloro-2- (trifluoromethyl)-1H-benzimidazole with modified cyclodextrins
T2 - Implications for physicochemical properties and antiparasitic activity
AU - Rojas-Aguirre, Yareli
AU - Castillo, Ivan
AU - Hernández, David J.
AU - Nogueda-Torres, Benjamín
AU - Márquez-Navarro, Adrián
AU - Villalobos, Juan C.
AU - Sánchez-Bartéz, Francisco
AU - Sánchez-Torres, Luvia
AU - Gracia-Mora, Isabel
AU - Castillo, Rafael
AU - Hernández-Luis, Francisco
N1 - Funding Information:
We are grateful to Margarita Portilla, Elvia Reynoso and Cecilia Salcedo from Facultad de Química, USAI, UNAM, for the determination of DSC thermograms and powder X-ray diffractograms, and Beatriz Quiroz-García from IQ, UNAM, for assistance with NMR spectroscopy. This study was supported by grants from PAPIIT-UNAM IN210809 and CONACyT 80093 .
PY - 2012/1/4
Y1 - 2012/1/4
N2 - The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H- benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job's plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host-guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2.
AB - The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H- benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job's plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host-guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2.
KW - Benzimidazole
KW - Cyclodextrins
KW - Leishmania mexicana
KW - Supramolecular association
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=80054743849&partnerID=8YFLogxK
U2 - 10.1016/j.carbpol.2011.08.009
DO - 10.1016/j.carbpol.2011.08.009
M3 - Artículo
SN - 0144-8617
VL - 87
SP - 471
EP - 479
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
IS - 1
ER -