202
A. V. Velikorodov and L. T. Sukhenko
TABLE 1. Antimicrobial Properties of N-Arylcarbamates I–XII
strains of St. aureus 209 and E. coli O18 and with cultures of
these microbes isolated from humans. The resistance of the
cultures of conditionally-pathogenic human microflora with
respect to the synthesized compounds was studied by direct
diffusion into a nutrient medium (meat-infusion broth) and
by the method of paper disks in Petri dishes preliminarily in-
oculated with suspensions of the isolated microorganisms
(diluted to 1 ´ 105 microbial cells per ml). Compounds
I – XII were introduced in 25 ml aliquots into wells with nu-
trient medium, starting with a concentration of 1 mg/ml (sol-
vent, DMSO). The samples of microbe cultures with tested
compounds were incubated at 37°C.
Diameter of retarded microbial growth zone, mm
Com-
St. aureus 209 Micrococcus1
E. coli O18
14.0 ± 1.7** 13.8 ± 2.0**
E. coli1
pound
I
…
…
II
0
0
0
0
12.0 ± 0.5*
13.0 ± 0.8**
18.0 ± 1.6**
5.5 ± 0.1*
III
IV
V
0
0
0
24.8 ± 3.2***
0
19.8 ± 0.05** 22.4 ± 0.01*** 2.4 ± 0.2*
17.0 ± 0.08** 25.0 ± 0.05*** 16.6 ± 2.75**
VI
VII
VIII
IX
X
…
0
0
30.0 ± 0.1*** 21.0 ± 0.05**
10.0 ± 0.05*
22.4 ± 0.5***
0
10.5 ± 0.1*
18.0 ± 0.1**
The microbe sensitivity to the drugs was evaluated by
measuring the diameter (in mm) of the zone of retarded mi-
crobial growth around each well (with allowance for the well
diameter) [7]. The observations made every two days over a
period of two weeks gave a pattern of stable or suppressed
microbial growth and the dynamics of decrease in the activ-
ity of compounds. The reference drug was gentamicin. In ad-
dition, the drug resistance of the microbial cultures studied
was assessed and rated according to the conventional classi-
fication [8].
20.0 ± 0.1**
22.1 ± 0.09*** 11.5 ± 3.8*
8.7 ± 0.8*
27.1 ± 0.1*** 25.5 ± 1.4***
2.2 ± 0.3*
XI
XII
7.8 ± 0.1*
14.0 ± 0.1**
12.0 ± 0.03*
15.0 ± 1.09** 9.8 ± 1.08*
…
…
12.8 ± 0.08*
Gentam
icin
…
38.6 ± 0.08*** 36.2 ± 0.06*** 18.0 ± 1.5**
Notes: 1 Microbes isolated from a patient with acute respiratory vi-
ral disease; rated microbe resistance: (0) stable growth, (*) low sen-
sitivity, (**) medium sensitivity, (***) high sensitivity.
It was established that a most pronounced antimicrobial
activity in the series of compounds studied is inherent in
compounds VI, VII, IX, and X containing nitro groups in
ortho positions relative to the carbamate group. The activity
of compounds VI, VII, IX, and X correlates with the s-con-
stants of substituents (Me, OMe, H, NHCO2Me) in para po-
sitions to the carbamate fragment [9].
was poured into 25 ml of ice-cold water, carefully acidified
with concentrated hydrochloric acid to an acid reaction, and
extracted with chloroform (2 ´ 250 ml). Then the solvent
was distilled off in a rotor evaporator; during this process,
the residue exhibits crystallization. Finally the product is
recrystallized from ethanol to obtain 14.6 g (61%) of com-
pound XIII in the form of a white powder; m.p., 126°C;
C10H12N2O5; IR spectrum (nmax, cm – 1): 3300 – 3420 (NH,
OH), 1715 (C=O), 1620, 1575 (C–C arom).
REFERENCES
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M e t h o d B . To 1.5 g (7 mmole) of nitro compound XI
in 20 ml of methanol, cooled on ice, was added by portions
with stirring 4 g (23 mmole) of sodium dithionite in 20 ml of
a 7% aqueous ammonium hydroxide solution. When the so-
lution discolored, a small amount (0.05 g) of sodium
dithionite was added and the reaction mixture was stirred for
0.5 h and allowed to stand in the cold for 1 h. The precipitate
was separated by filtration, washed with water, dried, and
acylated with methyl chloroformate in an aqueous sodium
hydrocarbonate solution. This yielded a crystalline product
with m.p. = 126°C, identical to the substance obtained by
method A.
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EXPERIMENTAL BIOLOGICAL PART
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The antimicrobial activity of N-arylcarbamates I – XII
was determined by testing with standard staphylococcal