Metal (II) Complexes of Fluconazole: Thermal, XRD and Cytotoxicity Studies

Document Type: Research article

Authors

1 Department of Applied Chemistry and Chemical Technology, Faculty of Science, University of Karachi, Karachi-75270, Pakistan.

2 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA.

3 Department of Chemistry, Faculty of Science, University of Karachi, Karachi-75270, Pakistan.

4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Karachi-75270, Pakistan.

5 Industrial Analytical Center (ICCBS), University of Karachi, Karachi-75270, Pakistan.

6 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

7 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

We report thermal, X-ray diffraction (XRD) and cytotoxicity studies of complexes of fluconazole (FCZ) with Cu (II), Fe(II), Cd(II), Co(II), Ni(II), and Mn(II). From XRD measurements, FCZ and its metal complexes were identified as polycrystalline. Marked differences in the X-ray patterns of drug and its metal complexes revealed that the complexes are indeed different compounds and not just the mixture of the starting materials. Unlike pristine FCZ, which did not exhibit cytotoxicity, three complexes derived from Fe(II), Cu(II) and Co (II) proved to be effective in the cytotoxicity assay. The Cu(II)-FCZ exhibited significant activity against SNB-19, HCT-15, COLO-205, and KB-3-1 cell lines, while Fe(II)-FCZ and Co(II)-FCZ were found cytotoxic only to KB-3-1 cell line. For the pure FCZ, thermogravimetry revealed massive weight loss in the temperature range of 215 to 297 °C, due to the volatilization of FCZ. All the complexes followed multi-stage degradation profiles, eventually resulting in the formation of metal oxides. For pure FCZ, differential scanning calorimetry revealed melting point at 137°C, followed by two further endothermic transitions at 294 °C and 498.44 °C representing the volatilization and subsequent degradation of FCZ, respectively. The absence of endothermic FCZ melting peak at around 137 °C indicates that the complexes represent different compounds. All complexes exhibit endothermic transitions at around 240-300 °C, representing melting and removal of ligand moiety, followed by another endothermic transition at around 498-499 °C, representing the ligand decomposition.

Graphical Abstract

Metal (II) Complexes of Fluconazole: Thermal, XRD and Cytotoxicity Studies

Keywords