Antimicrobial Activities of Schiff Base Metal Complexes of First Transition Series

The correlative antimicrobial analysis of amino acid Schiff base and derivatized tren metal complexes: A= [MLCl2], B= [ML(CH3OH)2], respectively, against fungal strains, Candida parapsilosis, Candida albicans, Candida krusei, and Cryptococcus neoformans and (Gram-negative) P. aeruginosa, E. coli, S. typhimurium, and S. pyogenes, Methicillin-resistant Staphylococcus aureus (MRSA), S. mutans (Gram-positive) bacterial strains had been done by disk diffusion method following McFarland protocol. [CuLCl2] and [Cu (CH3OH)2] manifest overwhelming activity against microbes than other metal complexes of cobalt, nickel and zinc. Minimum inhibition concentration data also shows that copper complexes have the lowest MIC values against these tested microorganisms. The significance of this investigation is to uncover shielding and constructive therapeutic agents that wield against bacterial and fungal infection.

In coordination chemistry, metal complexes derived from different Schiff base ligands are immanent, and they have played a significant role since the last decades. The derivatives of these ligands are pervasive because they are synthesized very easily and have vast applications. 1,2 . Metal complexes of the Schiff base ligand have expanded extensively due to their meaningful biological, catalytic, and fluorescence activities 3,4 . Schiff bases offer a broad range of biological activities 5,6 for which the imine or azomethine group existing in their edifices plays a vital role 4,7 to contribute in bioinorganic sciences; consequently,,, many Schiff base metal complexes are synthesized and assessed for their antifungal and antibacterial activities. The escalating rate of fungal and bacterial strains that ensue resistance to classical antibiotics has reinforced the researchers to develop new antibiotic compounds. Owing to the presence of azomethine (-C=N-) functional group, it gets bonded with two or more biologically active heterocyclic or aromatic compounds to form various types of molecular hybrids possessing excellent antimicrobial properties. These Schiff bases are chelating agents that generally coordinate with metals, especially with d-block metals and lanthanides, and form stable chelates with vast therapeutic applications [8][9][10] . These Schiff bases create a new type of prospective antimicrobial and anticancer reagents 11 . Some Schiff base metal complexes, derived from halogenated salicylaldehyde, have enormous applications in a diverse field of study related to luminescent probes, anti-HIV antimicrobial, antitumor, bio-catalysts in DNA and RNA cleavage reactions 12 due to the excellent coordination with metal ions. These derivatized complexes are also used as fungicides, insecticides, flavoring agents for the bouquet and liquor 13,14 .
In this paper, we report the invitro antifungal and antibacterial activity of  2 ]. The experimental antimicrobial analysis was performed by using the disk diffusion method 15 . In this method, the antimicrobial impregnated disk is placed on an agar medium previously inoculated with the test microorganism that picks up the moisture, and the antibiotic diffuses radially through the agar medium producing an antibiotic concentration gradient.

Chemicals and starting materials
A n a l y t i c a l g r a d e s o l v e n t s and reagents were used throughout the experiment.  2 ] were prepared according to our last published work [1]. These metal complexes [M= Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ ] were synthesized from ligand [L 2 ] derived from l-leucine and glyoxal, and the template reaction was carried out in a 1:1:1 ratio. (Scheme 2) Disk diffusion method Disk diffusion method was used for antimicrobial activity of these complexes against bacterial and fungi strains. The microbial inoculums were performed on Brain Heart Infusion (BHI) medium incubated at 37! for 18hrs, and Sabouraud Dextrose broth (SDB) medium incubated at 35! for 24hrs for bacterial and fungal strains, respectively and were homogenously distributed onto sterilized petri dishes. The inoculum density of each microorganism was standardized with 0.5 McFarland standards (following McFarland protocol), the suspension had a final inoculum of 10 5 and 10 6 CFUml -1 (colony-forming unit), respectively. Now the saline suspension of 10ìL was mixed with 10milliters of sterile antimicrobial agar at 40!. Five Whatman filter paper no. 1 disks of 6.0 mm diameter were placed on 9 cm diameter nutrient agar (NA) plates. Then the microorganisms were individually loaded on the surface of the disks. A blank disk was soaked in the solvent (DMSO) and entrenched as a negative control with no inhibitory region on each plate along with the standard drugs. These testing complexes diffuse into the agar and inhibit the growth and germination of the test microorganism, and then the diameters of inhibition growth zones that emerged around the samples disk were measured in millimeters. in Vitro-Antimicrobial activity In order to analyze the antibacterial activity, the stock solution was prepared by dissolving 1mg of the test metal complex in 100ìl of DMSO.

resUlts And disCUssion
All the metal complexes reveal antimicrobial activity, and they were found to be active inhibitors against bacterial strains. (Table1, 2) and fungal strains (  Tables 1 and 2 shows the antibacterial activities of four different metal-ligand complexes against the gram-negative and gram-  2 ] complexes were most active against the fungal strains and showed the highest activity against C. krusei (i.e., 19.0±1.2 and 18.5±1.3 respectively). The activity is greatly enhanced at higher concentrations. DMSO (-ve control) has shown   figures 1-4), it was found that fewer amount of copper complexes will be required for inhibiting the growth of the organism and can act as a conspicuous antimicrobial agent.
Complexes of copper exhibit analogously more inhibition compared to antibiotics used. MIC data in figures 1, 2, 3 and 4 show that copper complexes have proved to be the most active against the microbes tested at the concentrations used. The high antibacterial and antifungal activity of the copper complexes can be explained by the fact that the process of normal cells gets affected due to the copper ions. Therefore, the polarity of such metal ions decreases because the partial +ve charge on these metal ions attached with the donor groups of the ligands delocalizes the electrons over the entire chelating ring during the complexation reaction 17 ; as a result, the central metal atom shows increased lipophilic character due to which it infiltrates with high affinity in the microorganisms via a lipid layer of the cell membrane.

ConClUsion
Schiff base ligands are privileged ligands because they are prepared by a simple condensation of primary amines and aldehydic derivatives. These metal-based Schiff base chelates have significant biological properties for modification towards future drug development as microorganisms invalidate current antimicrobial agents effectiveness through many adaptations and resistance.
In The apparent distinction of antibacterial and antifungal activities of these derivatized compounds verifies the purpose of this research work. Generally, copper coordination complexes, due to highly effective redox activity and the biogenicity of its ions, show numerous biological activities and are also very effective in treating fungal and bacterial infections [18][19][20]. The practical significance shows that such a compound may be more efficient against these microbes, for which a detailed analysis about their biological effects, toxicity can be more effective in devising antibacterial and antifungal agents for therapeutic use. Therefore, these new antimicrobial agents should efficiently possess a different mode of action to combat resistance in pathogenic species.