E.A. S¸ener et al. / Il Farmaco 55 (2000) 469–476
475
24 h at 2591°C. Testing was performed in Sabouraud
dextrose broth at pH 7.4 and the two-fold serial dilution
technique was applied. The final inoculum size was 104
CFU/ml. A set of tubes containing only inoculated
broth was kept as controls. After incubation for 48 h at
2591°C, the last tube with no growth of yeast was
recorded to represent MIC expressed in mg/ml.
2a, 2b, 2f, 2g, 2h and 2k with their heterocyclic ana-
logues 3–8 [1,2,7], assuming that they are the possible
metabolites of benzoxazoles as given in Table 3.
Table 3 reveals that although most of the benzoxazole
derivatives (3–8) show better antimicrobial activity than
the corresponding amides, some amide derivatives pos-
sessed either the same or one-fold improved potency.
This is the case of compound 2f which showed one dilu-
tion better antibacterial activity than the compared ben-
zoxazole derivative 5 against S. faecalis and K.
pneumoniae. Additionally, compounds 2a and 2b
showed the same activity as benzoxazole derivatives 3, 4
against the tested two Gram-positive bacteria and E.
coli.
As far as activity is concerned, most of the synthe-
sized compounds were as potent as the cyclic analogues
3–8, showing a MIC value of 25 mg/ml against C. albi-
cans, except 2f and 2k. While compound 2k showed
one-fold less potency than its cyclic analogue, com-
pounds 2f and 2h showed better antifungal activity than
the compared benzoxazole derivatives.
4. Results and discussion
The antimicrobial activity of these compounds and
the control drugs is shown in Table 2 indicates that the
compounds 2a–2p were able to inhibit in vitro growth
of a number of microorganisms, exhibiting MIC values
between 50 and 12.5 mg/ml.
Table 2 reveals that the synthesized compounds
showed antibacterial activity at an MIC value of 50 mg/
ml against the Gram-positive bacteria S. aureus except
the derivatives 2e, 2f, 2i, 2j, 2k, which were active at 25
mg/ml. All the synthesized compounds possessed the
same potency, 50 mg/ml MIC value, against S. faecalis.
The activity of the compounds 2a–2p was also tested
against E. coli, K. pneumoniae and P. aeruginosa as
Gram-negative bacteria. These compounds, against E.
coli and K. Pneumoniae, exhibited lower potency than
the control drugs tetracycline and streptomycin, but
they showed the same potency as erythromycine. The
In conclusion, antimicrobial activity data reported in
Table 3 suggest that the pharmacophoric groups in
these sets of amides and cyclic analogues could be simi-
lar. If these amides are the possible metabolites of the
corresponding fused heterocyclics, then we can expect
prolonged antimicrobial activity for these derivatives.
compound
4-amino-N-(2%-hydroxyphenyl)benzamide
(2g) was the most active against K. pneumoniae (MIC
value of 25 mg/ml).
Acknowledgements
As regards antibacterial activity against the enter-
obacter P. aeruginosa, the synthesized compounds 2e–
2g, 2i–2o showed significant activity (25 mg/ml MIC
value) and possessed better potency than the control
drugs streptomycin and tetracycline and showed the
same activity as erythromycine and chloramphenicol.
Moreover, the antifungal activity of the synthesized
compounds was tested against C. albicans and MIC val-
ues between 25–12.5 mg/ml were found. Compounds 2e,
2h, 2m were found more active than the other com-
pounds, showing a MIC value of 12.5 mg/ml. However,
the control drugs oxiconazole and haloprogin possessed
one dilution better potency than these compounds.
Benzamides 2d–2p were found more active than
phenylacetamides 2a–2c, in particular against Gram-
positive bacteria S. aureus, Gram-negative bacteria P.
aeruginosa and the fungus C. albicans. When the MIC
values of 2a–2c are compared with the previously syn-
thesized phenylacetamides [14] against C. albicans, it is
observed that substitution with an atom and/or atom
groups at position R3 possessing electronically positive
field effects, such as Cl, Br and NO2, increases their anti-
fungal activity.
We would like to thank the Research Fund of Ankara
University (Grant No. 92-03-00-02) for financial sup-
port of this research.
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