Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide

Abstract

Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.