Synthesis, characterization, antibacterial, antifungal and immunomodulating activities of gatifloxacin–metal complexes Najma Sultana a , Asia Naz a,d, * , M. Saeed Arayne b , M. Ahmed Mesaik c a Research Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Karachi 75270, Pakistan b Department of Chemistry, University of Karachi, Karachi 75270, Pakistan c Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Centre for Chemical Sciences, University of Karachi, Karachi, Pakistan d Ziauddin College of Pharmacy, Ziauddin University, Karachi, Pakistan article info Article history: Received 7 July 2009 Received in revised form 29 December 2009 Accepted 19 January 2010 Available online 25 January 2010 Keywords: Gatifloxacin Metal complexes Spectroscopic techniques Antibacterial studies Anti-inflammatory and immunosuppressive activities abstract Gatifloxacin is a potent fluoroquinolone antibacterial agent. It is reported and our previous work has also proved that availability of gatifloxacin is reduced by co-administration of metallic supplements. For bet- ter understanding of these interactions, complexes of gatifloxacin were synthesized with Mg(II), Ca(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) (usually present in human body) and their structures were established with the help of spectroscopic studies like IR, UV, and NMR. The IR spectra of the complexes suggest that the gatifloxacin behaves as a monoanionic bidentate ligand. In vitro anti- bacterial, antifungal, anti-inflammatory and immunosuppressive activities of the gatifloxacin and the complexes were tested. GTX-Ni and GTX-Cu has excellent anti-inflammatory activity. Ó 2010 Elsevier B.V. All rights reserved. 1. Introduction Gatifloxacin sesquihydrate (GTX) or 1-cyclopropyl-6-fluoro-1,4- dihydro-8-methoxy-7-[3-methyl-1-piperazinyl]-4-oxo-3-quino- linecarboxylic acid (Fig. 1), is a synthetic broad-spectrum antimi- crobial fluoroquinolone active against both Gram-negative and Gram-positive organisms and is used in the treatment of a wide range of infections [1]. It is believed that methoxy group mediates the binding of the DNA–DNA gyrase complex to the DNA-topoiso- merase complex and potentially decreases the likelihood of high- level resistance [2]. The mechanism of gatifloxacin action involves inhibition of bacterial DNA gyrase, which is essential for DNA rep- lication, and it has been proposed that metal complex intermedi- ates are involved in this process [3,4]. A study on the structure and activity of certain quinolones and the interaction of their Cu(II) complexes on a DNA model, suggested that the intercalation of the quinolone complexed to a metal is an important step in the mech- anism of action of these drugs [5]. Number of studies confirmed that DNA-affinity of the quinolone, modulated by Mg (II), plays an important role in poisoning the cleavable gyrase-DNA complex and, consequently, in eliciting antibacterial activity by this family of drugs [6]. Many drugs have modified pharmacological and tox- icological properties in the form of metal complexes and the Cu(II) complexes of drugs have proved useful in several diseases such as gastric ulcers, rheumatoid arthritis, tuberculosis and cancers [7– 10]. These results encouraged us to study the coordination chem- istry of antibiotics and compounds with transition and d 10 metal ions in an attempt to determine the modes of binding in the solid state and to investigate biological activities. As a continuation of our work on metal interactions with fluoroquinolone derivatives [11] we describe the synthesis and characterization of complexes of gatifloxacin with Ni(II), Cu(II), Zn(II), Cd(II), Fe(III), Ca(II), Mg(II), Cr(III), Mn(II) and Co(II) using conductometric, spectral (UV, IR and 1 H-NMR) measurements though some of gatifloxacin–metal com- plexes are already repotted in literature but their biological activ- ities were not studied in detail [12,13]. We include data on the antibacterial, antifungal and immunomodulatory activities of me- tal complexes of gatifloxacin. 2. Materials and methods Barrette Hodgson Pakistan, Pharm Evo, Abbott Pakistan provided gatifloxacin sesquihydrate, gemifloxacin mesylate and sparfloxacin, respectively. Metal salts and methanol were purchased from Merck Germany. Other chemicals used were of analytical grade and water used was twice distilled. IR studies were carried out with Shimadzu 0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2010.01.036 * Corresponding author. Address: Research Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Karachi 75270, Pakistan. Tel.: +92 21 3323117226. E-mail address: malik_asianaz@hotmail.com (A. Naz). Journal of Molecular Structure 969 (2010) 17–24 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc