M. S. Iqbal  ( Pakistan Atomic Energy Commission, Islamabad. )
S.J. Khurshid  ( Nuclear Chemistry Division, Pakistan Institute of Nuclear Science and Technology, Islamabad. )
M. Z. Iqbal  ( Institute of Chemistry, University of the Punjab, Lahore. )

Copper complexes of L-alanine, L-arginine, L-histidine, L-lysine, L-proline and L-threonine were studied for their antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes and Esáherichia Coli. The complexes of 1 -alanine, 1 -proline and 1 -threonine were nearly as active as ampicillin against Strep. Pyogenes. Mixed complexes of these amino acids showed similar effect. Other complexes were also active to a significant extent against all the three strains studied (JPMA 40 : 221, 1990).
Copper-amino acid complexes have been shown to possess anti- inflammatory (AI) activity¹. The mode of action of such complexes is not yet clear. However, in the past some of the AI drugs used have been those basically developed as antibacterials. For example gold compounds used in the treatment of rheumatoid arthritis inhibited the growth of tubercule bacilli³, Depsone⁴, Indomethacine⁵, Levamisol⁶ and Pencillamine⁷ being standard prescrip­tions to combat severe rheumatoid arthritis, are known to have antibacterial activity. Some of the copper complexes have also been studied against mycoplasma infections but no systematic study has been carried out in this regard^8,9. In this communication we report a study of the antibac­terial activity of copper-amino acid complexes to under­stand their mode of action.

Copper-amino acid complexes were pepared in solution form according to the usualmethod^10,11 mixing 2m mol of amino acid and immol of copper acetate in water. The blue solutions thus obtained were used for testing antibacterial activity. The mixtures of copper complexes were prepared by mixing two parts of amino acid and one part of copper salt in water. The amino acids used were L-alanine, L-arginine, L-bistidine, L-proline and L- threonine. The solution of the complexes were tested for theft antibacterial activity both individually and as admixtures. The complexes of L-alanine, L-proline and L-threonine used in admixtures were selected because they showed significant activity when tested individually. In each case the solution containing equivalent to 10 ug of the complex was loaded on the susceptibility disc and the activity was measured against Staph. aureus, Strep. pyogenes and E. coli in the blood agar and Muller Hinton medium using ampicillin (10 ug) disc as standard according to the standard susceptibility testing method12. The sensitivity of copper acetate and the amino acids (10 ug) each was measured separately.

The sensitivity results are listed in Table.

All the amino acids tested were resistant. The activity shown by most of the copper-amino acid complexes is greater than that of copper salt indicating that the complexes possess significant antibacterial activity against the strains tested. The copper complexes of alanine, proline and threonine showed antibacterial activity only against streptococcus pyogenes comparable to that of ampicillin, whereas com­plexes of arginine, histidine, lysine showed less activities against these strains. The three mixed complexes of alinine, proline and threonine have also shown similar effects. From these results it appears that the hypothesis postulating the partial role of antibiotic activity of Al drugs in combating inflammation may be substantive. The knowledge of antibacterial activity of the copper-aminoacid complexes gained through this study, and their possible effectiveness in inflammation strengthens the speculated role of bacterial patbogens in such type of ailment particularly in rheumatoid arthritis¹³, and also provides an insight into theft mode of action.

1. Jackson, G.E., May, P. M. and William, D. H. Metal-Ligand com­plexes involved in rheumatoid arthritis-i. J. Inorg. Nucl. Chem., 1978; 40: 1189.
2. Sorenson, J.R.J. Inflammatory diseases and copper. New Jersy, Humana Press, 1982, p. 289.
3. Koch, it Antibacterial action of gold salts. Deuttsche. Med. Woreheusher, 1927; 16: 756.
4. Toodman, L.S. arid Oilman, A. The pharmacological basis of therapeutics. 4th ed. New York, Macmillan, 1970, p. 1311.
5. Plant, J.E., Higgs, G.A. and Easmon, C.S. Effect of antiinflam­matory agents on chronic Salmonella typlumuriam infection in a mouse model. Infect. Immun., 1983; 42: 71.
6. Lozada, F., Silverman, S. and Cram, D. Phemhigusvulgaris. Astudy of six cases treated with levamisole and prednisone. Oral. &irg., 1982; 54 : 161.
7. Vinnik, L. A., Vishnevetskii, F. E. and Perbukhin, Iu. V. Effect of D-Pencillamine on experimental tuberculosis. Probl. Tuberk., 1980; 3:64.
8. Brown, T.M., Baily, J.S., Iden, I.I. and Clark, H.W. Inflammatory diseases of copper. New Jersey, Humana Press, 1982, p. 391.
9. Mukhammud Zhanov Kh, K. Effect of some Trace Elements com­plexes on, E. Coli and Staph. aureus. Med. Zh. Uzb., 1985; 3 : 45.
10. Aberhalden, E. and Schnitzler, E. Copper salts of amino acids and polypeptides. Z. Physiol. Chem., 1927; 163: 94.
11. Sorenson, J. it Copper chelatcs as possible active forms of the antiarthritic agents. J. Med. Chem., 1976; 19: 135.
12. Bauer, A. W., Kirby, W. M. M., Sheris,J.C. and Turck, M.Antibiotic susceptibility testing by standardized single disc method. Am. J. Clin. Pathol., 1966; 45 : 493.
13. Pullar, T., Hunter, J.A. and Capell, H. A. Which Component of sulphasalazine is active in rheumatoid arthritis? Br. Med. J., 1985; 290 :1535.