Synthesis, characterization and biological activities of cephalosporin metals complexes

Abstract

Cephalosporin is widely used group prescribed as broad-spectrum antibiotic, containing β-lactam ring. Numerous different bacteriological pathogens are now resistant against cephalosporin due to over use. Subsequently it is necessary to synthesize new derivatives to enhance **biological activity** against pathogens. In current study cephalosporin were reacted with essential trace elements to synthesize respective metal complexes. The novel compounds were characterized at different spectroscopic techniques like UV, FTIR, HPLC and AAS (atomic absorption spectroscopy). Biological screening of novel compounds was accomplished against diverse group of pathogens. Some of our novel compounds showed high efficacy against the pathogens as compare to parent composites. We have introduced Novel method for ceftriaxone assays at HPLC using simple and safe mobile phase through metal complexation. Toxicity studies were carried out in vitro and with ADMET software. Novel complexes were found less toxic as compare to parent compounds.

Introduction

Cephalosporin antibiotics consist of variety of compounds having different spectrums of activity and pharmacokinetics. All members of this group are derived from cephalosporin C which is obtained from Cephalosporium acremonium. Cephalosporins are bactericidal and act by restricting mucopeptide synthesis resulting defective cell wall. Definite mechanism is not fully known but their Beta lactam ring binds with several enzymes like corboxypeptidases, endopeptidases and transpeptidases which are involved in cell wall synthesis (Anacona et al., 2013). Different spectrums of activity are shown due to different affinity of beta lactam antibiotics toward enzymes. Cephalosporin is wideranging class of antibiotics conferring to its efficacy against gram positive and gram negative pathogen, grouped in four generations. Group four is broad spectrum antibiotics works thriving against both grams positive and grams negative.

Cephalosporins are abundantly used as broad spectrum antibiotics. According to the WHO china alone consumes more than 1000 ton/anum. Most of the microbes became resistant to cephalosporin due to heavy usage (Jacoby, 2005). Ciprofloxacin has been reported resistant against Escherichia Coli strain in Beijing Hospitals (Wang et al., 2001). Streptococcu spneumonia is resistant to most of the Cephalosporins (Davidson et al., 2002). Gonorrhea infection has also been reported resistant to fluoroquinolones. (Newman et al., 2004). Salmonella, Shigella, and Campylobacter species has also been reported resistant tocephalosporins. (Alfredson and Korolik, 2007) Keeping this special issue with Cephalosporin we are interested to change the chemistry of this value molecule.

It has been observed that complexation reduces the toxicity of drugs Pathogens are more sensitive to metal complexes as compared to parent compounds (Auda et al., 2008). The molecular diagram indicates cephalosporin possesses– NH2,- COOH,- CO and N-C and work as ligand. So it form chelatecomplex with essential trace elements like Iron, zinc, cobalt, nickel and chromium (Reiss et al., 2014).

Metal complexes play important role in curing diseases e.g. Cu complexes are effective against, tuberculosis, cancer and rheumatoid arthritis (Williams, 1971).

Cisplatin frequently used in cancer therapy. Similarly Silver and Bismuth complexes show good efficacy against pseudomonas, breast cancer and ulcer respectively (Curran, 2009). Moreover, these ligands bind to essential trace elements in body and may decrease their bioavailability. Deficiency of these essential trace element in body may cause some physiological disorder (Chitterjea, 1993).

Aims of current study were Synthesis, characterization and predicting biological activities of Cephalosporin Metals Complexes. In our study most of essential trace elements like Fe, Zn, Cu, were coordinated with Ceftriaxone, Cefotaxime, Cefoperazone, Cefepimeand Ceftazidime. So intake of theses complexes reduces the risk of deficiency of this essential trace element in the body.

Source : Synthesis, characterization and biological activities of cephalosporin metals complexes