Characterization and structural analysis of the potent antiparasitic and antiviral agent tizoxanide

Bruno, FP; Caira, MR; Ceballos Martin, E; Monti, GA; Sperandeo, NR

HERO ID

2047494

Reference Type

Journal Article

Year

2013

HERO ID 2047494
In Press No
Year 2013
Title Characterization and structural analysis of the potent antiparasitic and antiviral agent tizoxanide
Authors Bruno, FP; Caira, MR; Ceballos Martin, E; Monti, GA; Sperandeo, NR
Journal Journal of Molecular Structure: Theochem
Volume 1036
Page Numbers 318-325
Abstract Tizoxanide [2-(hydroxy)-N-(5-nitro-2-thiazolyl)benzamide, TIZ] is a new potent anti-infective agent which may enhance current therapies for leishmaniasis, Chagas disease and viral hepatitis. The aim of this study was to identify the conformational preferences that may be related to the biological activity of TIZ by resolving its crystal structure and characterizing various physicochemical properties, including its experimental vibrational and C-13 nuclear magnetic resonance properties, behavior on heating and solubility in several solvents at 25 degrees C. TIZ crystallizes from dimethylformamide as the carboxamide tautomer in the triclinic system, space group P(-1) (No. 2) with the following unit cell parameters at 173(2) K: a = 5.4110(3) angstrom, b = 7.3315(6) angstrom, c = 13.5293(9) angstrom, alpha = 97.528(3), beta = 95.390(4), gamma = 97.316(5), V= 524.41(6) angstrom(3), Z = 2, D-c = 1.680 g/cm(3), R-1 = 0.0482 and wR(2) = 0.0911 for 2374 reflections. This modification of TIZ has a 'graphitic' structure and is composed of tightly packed layers of extensively hydrogen-bonded molecules. The various spectroscopic data [Diffuse Fourier transform infrared (DRIFT) and FT-Raman, recorded in the range 3600-500 and 4000-200 cm(-1) respectively, and solid-state C-13 NMR] were consistent with the structure determined by X-ray crystallography. From DSC, TG and thermomicroscopy, it was concluded that TIZ is thermally stable as a solid and that melting is not an isolated event from the one-step thermal decomposition that it undergoes above 270 degrees C. This modification of TIZ is practically insoluble in water and slightly soluble in polar aprotic solvents such as dimethylsulfoxide, dimethylformamide and dioxane. (c) 2012 Elsevier B.V. All rights reserved.
Doi 10.1016/j.molstruc.2012.12.004
Wosid WOS:000316091700044
Url http://linkinghub.elsevier.com/retrieve/pii/S0022286012011544
Is Certified Translation No
Dupe Override No
Comments Journal: ISSN:
Is Public Yes
Keyword Crystal structure; C-13 CPMAS NMR; DRIFT; FT-Raman; Thermal analysis; Tizoxanide