3. FOOD ChEMISTRy & bIOTEChNOLOGy 3.1. Lectures

Chem. Listy, 102, s265–s1311 (2008) Food Chemistry & Biotechnology
to be more active against Gram-positive than Gram-negative
bacteria (Pseudomonas aeruginosa).
In the case of Gram-negative isolate only complexes of
2-aminobenzimidazole derivatives exhibited significant inhibitory
activity. nickel (II) complexes of L 3 , L 4 and L 5 were
slightly active against the Pseudomonas aeruginosa. In the
case of Bacillus cereus and Staphylococcus aureus nickel
(II) complexes of ligands L 1 and L 2 also express higher activity
than another complexes. Gram-positive bacteria Sarcina
lutea was persistent in all investigated cases, too. nickel (II)
complexes containing L 1 and L 2 were very highly or highly
active, respectively. On the other hand, complexes of L 3 , L 4
and L 5 were moderately active against the same bacteria.
In the next phase, MIC of the tested compounds was
performed by the agar dilution method. From the results presented
in Table II, it is seen that nickel(II) complex containing
L 1 was active against Pseudomonas aeruginosa with a
MIC value of 250 µg ml -1 , whilst ni(L 2 ) 2 Cl 2 was less toxic.
However, ni(L 3 ) 2 Cl 2 and ni(L 4 ) 2 Cl 2 were same active, but
complex of L 5 has the low activity against the same bacteria.
In the case of Bacillus cereus and Staphylococcus aureus
complexes containing 2-aminobenzimidazole derivatives as
ligands were more active (MIC = 125 µg ml –1 ) than complexes
of 2-amino-5,6-dimethylbenzimidazole derivatives.
ni(L 3 ) 2 Cl 2 was equally active as ni(L 4 ) 2 Cl 2 with higher MIC
value of 250 µg ml –1 against the same bacteria, whilst complex
containing L 5 expressed MIC of 500 µg ml –1 .
On the other hand, all the complexes were more active
against Sarcina lutea. The complex of L 3 with a MIC value
of 125 µg ml –1 has the same activity as ni(L 4 ) 2 Cl 2 , but complexes
of 2-aminobenzimidazole derivatives were the most
active. ni(L 5 ) 2 Cl 2 has the lowest activity against these two
Gram-positive bacteria.
Comparing the activities of the tested complexes it was
found that 1-substituted-2-aminobenzimidazole derivatives
(L 1 , L 2 ) formed the nickel (II) complexes which were more
active than complexes of 1-substituted-2-amino-5,6-dimethylbenzimidazoles
(L 3 , L 4 , L 5 ). Consequently, it is suggested that
methyl groups at the 5 or 6 position decreases the general
inhibitory activity of the tested complexes. Also, antibacterial
results shows that if the benzimidazole nucleus was substituted
with a 3-chlorobenzyl group at the n1 atom, the antibacterial
activity was increased.
The differences found in the activities of the nickel (II)
complexes and the non-complexed ligands obtained in our
previous investigations 8 , suggest that the coordinated ni(II)
may play a significant role in the antibacterial potency. A
possible explanation may be offers by the chelation theory
stating a relationship between decreasing polarizability of
the metal and increasing lipophilicity of the complexes. This
property is now seen as an important parameters related to
membrane permeation in biological system. Many of the processes
of drug disposition depend on the ability or inability to
cross membranes and hence there is a high correlation with
measures of lipophilicity. Moreover, many of the proteins
involved in drug disposition have hydrophobic binding sites
s763
further adding to the importance of lipophilicity. The latter
might promote inhibitory activity.
Moreover, the results of this study revealing that the compounds
tested displayed higher activity against the Gram-positive
than the Gram-negative one bacteria, likely point to the
relevance of the structure of the bacterial cell wall in the antimicrobial
potency of the substances. It is prospective because
the cell wall is essential to the survival of many bacteria and
some antibiotics are able to kill bacteria by inhibiting a step in
the synthesis of peptydoglycan. Gram-positive bacteria possess
a thick cell wall containing many layers of peptidoglycan and
teichoic acids, but in contrast, Gram-negative bacteria have
a relatively thin cell wall consisting of a few layers of peptidoglycan
surrounded by a second lipid membrane containing
lipopolysaccharides and lipoproteins. These differences in cell
wall structure can produce differences in antibacterial susceptibility
and some antibiotics can kill only Gram-positive bacteria
and is ineffective against Gram-negative pathogens.
Table II
MIC tested of complexes
Complex
MIC [μg ml–1 ]
P.aeruginosa B. cereus S. aureus S. lutea
ni(L 1 ) 2 Cl 2 250 125 125 62.5
ni(L 2 ) 2 Cl 2 500 125 125 62.5
ni(L 3 ) 2 Cl 2 750 250 250 125
ni(L 4 ) 2 Cl 2 750 250 250 125
ni(L 5 ) 2 Cl 2 1000 500 500 250
Conclusions
The antibacterial activity of the nickel (II) complexes
with two series of 1-benzylbenzimidazole derivatives was
tested against very persistent microorganisms: Pseudomonas
aeruginosa, Bacillus cereus, Staphylococcus aureus and Sarcina
lutea. All the complexes displayed in vitro inhibitory
activity, but 1-substituted-2-aminobenzimidazole derivatives
formed the nickel (II) complexes which were more active
than complexes of 1-substituted-2-amino-5,6-dimethyl-benzimidazoles.
The basic antibacterial activity of the benzimidazoles
was produced by the presence of an amino group at
the position 2 of the benzimidazole ring. Methyl groups at
the 5 or 6 position decreases the general inhibitory activity of
the relevant benzimidazoles. Also, the results indicated that
tested complexes were more active against Gram-positive
than Gram-negative bacteria. It may be concluded that the
antibacterial activity of the compounds is related to cell wall
structure of the bacteria. It is possible because the cell wall is
essential to the survival of many bacteria and some antibiotics
are able to kill bacteria by inhibiting a step in the synthesis of
peptidoglycan.
This work has been supported by Ministry of Science
and Environment Protection of the Republic of Serbia as are
the part of the project No. 142028.