Schiff base ligands derived from phenylenediamine and its metal complexes as enhancer against two mechanisms of antibiotic resistance

The increasing mortality rate caused by serious infection due to widespread emergence of multidrug resistance microorganisms that are highly resistance to current available antibiotic can make the treatment of infectious diseases become difficult and ineffective. Therefore, the development of new antibacterial agents with potent and broad antibacterial activity with minimum toxicity is urgently needed. Schiff base are formed from the condensation reaction between primary amine reacts with aldehyde or ketone-like compounds under specific conditions and exhibit wide range of biological activities. Antimicrobial activity of 41 Schiff base compounds was analyzed against three strains of Gram-positive bacteria, Staphylococcus aureus (ATCC 25923), Staphylococcus haemolyticus (ATCC 29970), and Staphylococcus cohnii subsp.urealyticum (clinical strain); and four strains of Gram-negative bacteria, Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 10145), Klebsiella pneumonia (ATCC 700603), and Shigella flexneri (ATCC 12022) using resazurin microtiter based assay [1]. Schiff base compound Ovan(me)MPD and its tetranuclear metal complexes showed the highest percentage inhibition at 51.3 %. The synergistic effects of Schiff base on the susceptibility of K. pneumoniae and P. aeruginosa to antimicrobial agents with or without PAβN (Phe-Arg-β-naphtylamide) were measured. The MICs of chloramphenicol, nalidixic acid, gentamicin, tetracycline and streptomycin in the presence of PAβN, were significantly reduced, decreasing to 30–16 µg / mL. The effects of PAβN on the susceptibility of bacteria to Schiff base indicate that some that some Schiff base compounds are substrates for efflux pumps in Gram-negative bacteria and the presence of more metal centers in structure of Schiff base could increase the susceptibility of antimicrobial agent activity.

• References

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