Original article Synthesis, characterization and antibacterial activity of cobalt(III) complexes with pyridineeamide ligands Anurag Mishra a , Nagendra K. Kaushik b , Akhilesh K. Verma b , Rajeev Gupta a, * a Department of Chemistry, University of Delhi, Delhi e 110 007, India b Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi e 110 007, India Received 5 May 2007; received in revised form 16 July 2007; accepted 9 August 2007 Available online 14 September 2007 Abstract The ligands 2-(N-(X-pyridyl)carbamoyl)pyridine (X ¼ 2, 3 or 4 for HL 1 eHL 3 , respectively) and 2,6-bis(N-(Y-pyridyl)carbamoyl)pyridine (Y ¼ 2, 3 or 4 for H 2 L 4 eH 2 L 6 , respectively) in their mono- and di-deprotonated forms have been used to synthesize kinetically stable cobalt(III) compounds [Co(L 1e3 ) 3 ](1e3) and Na[Co(L 4e6 ) 2 ](4e6), respectively. The Co(III) ion is in octahedral environment and is surrounded by three bidentate ligands in complexes 1e3 and two tridentate ligands in complexes 4e6. Ligands coordinate the cobalt center via amidic-N and pyr- idine-N centers forming a 5-membered chelate ring. Complexes 1e6 have thoroughly been characterized by the various spectroscopic analyses ( 1 H NMR, 13 C NMR, UVevis, IR, mass), elemental analysis, and conductivity measurement. All complexes have been assayed for in vitro an- timicrobial activity against clinically isolated resistant strains of Pseudomonas, Proteus, Escherichia coli and standard strains of Pseudomonas aeruginosa (MTCC 1688), Shigella flexneri (MTCC 1457), Klebsiella planticola (MTCC 2272). All cobalt compounds show mild to moderate activity. However, complexes [Co(L 1 ) 3 ](1) and Na[Co(L 4 ) 2 ](4) were found to have potent activity against standard and pathogenic resistant bacteria used in the study. Their MIC ranged from 2.7 to 187 mg/ml. In vitro toxicity tests demonstrated that all complexes were less cytotoxic than that of gentamycin on HEK cell lines and the results reveal that these complexes can act as potent antimicrobial agents. Ó 2007 Elsevier Masson SAS. All rights reserved. Keywords: Cobalt complexes; Pyridineeamide ligands; Antibacterial activity; Cytotoxic activity; MTT assay 1. Introduction Emergence of resistance in bacterial strains has become as one of the prime concerns of the 21st century. There are serious concerns that untreatable pathogens may develop at an alarm- ing rate in the near future. Strategies to address this challenge include the design of improved versions of antibacterial classes already in clinical use and the use of drug combinations. The application of these strategies can be quite successful, but a high risk of rapid resistance development remains [1e3]. Thus, an urgent need for new potent classes of antibiotics with novel modes of action persists. Resistance in bacteria can result from the modification of an antibacterial target or from functional bypassing of that target, or it can be contingent on impermeability, efflux or enzymatic inactivation of the drug [4]. In light of these problems, the search for new antibacterial agents has gained immense popularity in the field of drug development. In this race of synthesizing new drugs, cobalt complexes have attracted a great deal of attention amongst the scientific community due to their therapeutic uses as tumor imaging agent [5], antitumor [6], transport protein transferrin (Tf) [5,6], antimycobacterial [7], antiischaemic [8], antiviral [9,10], antiparasitic [11], antithrombolytic [11], enzymatic therapeutics [11], anti-inflammatory activities [12] and as met- abolic modifier [13]. Herein we describe the synthesis and characterization of the novel Co(III) complexes as the poten- tial candidates for antimicrobial activity against standard as well as clinically isolated resistant bacterial strains with di- minished cytotoxicity on the HEK cell line. * Corresponding author. Tel.: þ91 11 2766 7624; fax: þ91 11 2766 6605. E-mail address: rgupta@chemistry.du.ac.in (R. Gupta). 0223-5234/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2007.08.015 Available online at www.sciencedirect.com European Journal of Medicinal Chemistry 43 (2008) 2189e2196 http://www.elsevier.com/locate/ejmech