Synthesis and structure elucidation of some new thioether derivatives of 1,2,4-triazoline-3-thiones and their antimicrobial activities.

Article abstract of DOI:10.1016/S0014-827X(01)01167-3

5-(4-Pyridinyl)-4-substituted-2.4-dihydro-3H-1,2,4-triazole-3-thiones and 5-(4-pyridinyl)-4-substituted-3-(benzoylmethyl)thio-4H-1,2,4-triazoles were synthesized. The structures of original nine compounds were confirmed by IR, 'H NMR, mass spectral methods and elemental analysis. The antibacterial, antifungal and antimycobacterial activities, together with those of known intermediate 1,4-disubstituted thiosemicarbazides, were reported.

Full text of DOI:10.1016/S0014-827X(01)01167-3

www.elsevier.com/locate/farmac
Il Farmaco 56 (2001) 953–958
Synthesis and structure elucidation of some new thioether
derivatives of 1,2,4-triazoline-3-thiones and their antimicrobial
activities
N.N. Gu¨lerman a, H.N. Dog˘an a, S. Rollas a,*, C. Johansson b, C. C¸ elik b
a Faculty of Pharmacy, Pharmaceutical Chemistry Department, Marmara Uni6ersity, Haydarpas¸a, Istanbul 81010, Turkey
b Faculty of Medicine, Microbiology Department, Marmara Uni6ersity, Haydarpas¸a, Istanbul 81010, Turkey
Received 25 October 2000; accepted 1 June 2001
Abstract
5-(4-Pyridinyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 5-(4-pyridinyl)-4-substituted-3-(benzoylmethyl)thio-
1
4H-1,2,4-triazoles were synthesized. The structures of original nine compounds were confirmed by IR, H NMR, mass spectral
methods and elemental analysis. The antibacterial, antifungal and antimycobacterial activities, together with those of known
intermediate 1,4-disubstituted thiosemicarbazides, were reported. © 2001 Elsevier Science S.A. All rights reserved.
Keywords: 1,2,4-Triazole derivatives; Synthesis; Antibacterial, antifungal; Antimycobacterial activities
1. Introduction
the thiosemicarbazides in alkaline medium [9,10] and
two compounds among them (2f and 2h) are original.
For the synthesis of 5-(4-pyridinyl)-4-substituted-3-
(benzoylmethyl)thio-4H-1,2,4-triazoles (3a–g), these
triazoles (2a–g) were reacted with phenacyl chloride in
acetone containing potassium carbonate, thus seven
original compounds were obtained (Scheme 1).
Certain 1,4-disubstituted thiosemicarbazide, 1,2,4-tri-
azoline-3-thione and 1,2,4-triazole-3-thiole derivatives
are of interest due to their bioactivity, including an-
tibacterial [1,2], antifungal [3,4] and antitubercular [5,6]
properties. We reported here on the synthesis and struc-
ture elucidation of 5-(4-pyridinyl)-4-substituted-2,4-di-
hydro-3H-1,2,4-triazole-3-thiones and 5-(4-pyridinyl)-
4-substituted-3-(benzoylmethyl)thio-4H-1,2,4-triazoles.
The microbiological tests were also applied to these
compounds and their known intermediate 1-(isonicoti-
noyl)-4-substituted thiosemicarbazides.
According to IR spectroscopic data of two original
compounds (2f, 2h) which have triazoline-3-thione
structure, the observation of CꢀS stretching bands of
1239 and 1261 cm−1 and the absence of an absorption
about in 2600–2550 cm−1 region cited for SH group
have proved that these compounds were in the thionic
form in the solid state [11,12]. NH stretching bands of
2f and 2h were observed at 3120 and 3500–3350 cm−1
,
2. Chemistry
respectively, and these bands disappeared in the IR
spectra of 3a–g. The IR spectra of thioether derivatives
(3a–g) showed CꢁS stretching bands in the 641–630
cm−1 region. The compounds (3a–g) showed charac-
teristic CꢀO stretching bands in the 1704–1674 cm−1
region. All data were consistent with the proposed
structures [11–13].
For the synthesis of 1-isonicotinoyl-4-substituted
thiosemicarbazides (1a–h), isoniazid was added to
ethyl, allyl, phenyl, p-(bromo/chloro/fluoro)phenyl,
benzyl and phenethyl isothiocyanates [3,7]. Isoniazid
was selected as the starting compound because of its
antitubercular activity [8]. 1,2,4-Triazoline-3-thione
derivatives (2a–h) were obtained by the cyclization of
1
In the H NMR spectra of 2f and 2h, NH peaks were
observed as a singlet at 14.35 and 14.15 ppm, respec-
tively, and so their thionic form was proved. Oppo-
sitely, NH signals were not observed in the H NMR
* Corresponding author.
E-mail address: sevim@sevimrollas.com (S. Rollas).
1
0014-827X/01/$ - see front matter © 2001 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(01)01167-3

954
N.N. Gu¨lerman et al. / Il Farmaco 56 (2001) 953–958
spectra of 3a–g. The methylene protons appeared as a
singlet at 4.81–5.03 ppm. Compound 3b showed cis
and trans separation of protons depending on the na-
ture of the allyl substituent [14]. Furthermore the sig-
nals of protons which characterized aromatic moiety of
3a–g, ꢁCH2CH3 protons of 3a and ꢁNCH2 protons of
3g were observed in the expected field and they are
consistent with those of IR and literature data [14–16].
The mass spectra of 3b, 3f and 3g which were selected
as prototype, showed molecular ion (M+) peaks, but
their relative intensities were very low. The mass frag-
mentation patterns of these compounds were shown in
Scheme 2.
trometer in DMSO with TMS as internal reference.
Mass spectra of 3b, 3f and 3g were obtained on a
Fisons Instruments VG Platform II LC-MS
spectrometer.
3.1.1. General procedure for the preparation of 5-(4-
pyridinyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazol-
3-thiones (2a–h)
Equimolar amounts of isoniazid and substituted
isothiocyanate were refluxed in ethanol for 3 h. The
precipitate (1a–h) was recrystallized from ethanol [7]
and then 0.0075 mol 1a–h dissolved 2N sodium hy-
droxide (15 ml), heated under reflux for 4 h [9]. After
cooling, the solution was acidified by hydrochloric acid,
the crude product was precipitated, filtered and washed
with distilled water. Pure compounds were obtained by
crystallization from ethanol or methanol.
3. Experimental
3.1. Chemistry
3.1.1.1. 4-(4-Fluorophenyl)-5-(4-pyridinyl)-2,4-dihydro-
3H-1,2,4-triazol-3-thione (2f). C13H9FN4S, m.wt. 272.3,
yellow crystals, 91% yield, m.p. 260–261 °C (EtOH).
Elemental analysis (%Calc./Found): 57.84/57.88 (C),
3.33/3.64 (H), 20.58/20.49 (N), 11.77/11.81% (S). IR (n,
cm−1): 3120 (NH triazoline); 3045 (ꢀCH aromatic);
1609, 1565, 1510, 1478, 1390 (CꢀC and CꢀN of rings);
1285 (CꢁN triazoline); 1239 (CꢀS); 1165 (ArꢁF); 830
(1,4-disubstituted benzene and 4-substituted pyridine).
Chemicals used in the experiments were commercially
available and were used without further purification.
All melting points were determined on a Buchi 530
melting point apparatus and uncorrected. The elemen-
tal analysis were performed on a Leco CHNS-932
instrument. IR spectra were obtained on a 1600 FTIR
spectrophotometer as KBr pellets. 1H NMR spectra
were obtained on a Bruker AVANC-DPX 400 spec-
Scheme 1. Synthetic route to compounds.

N.N. Gu¨lerman et al. / Il Farmaco 56 (2001) 953–958
955
Scheme 2. Mass fragmentations of 3b, 3f and 3g.
1H NMR, (l, ppm): 7.26 (2H, dd, J=6.14 Hz, C3H
and C5H of pyridine), 7.38 (2H, t, J=8.77 Hz, C3H
and C5H of phenyl), 7.48–7.52 (2H, m, C2H and C6H
of phenyl), 8.60 (2H, dd, J=6.02 Hz, C2H and C6H of
pyridine), 14.35 (1H, s, NH).
tate obtained by cooling was recrystallized from suit-
able solvent.
3.1.2.1. 4-Ethyl-5-(4-pyridinyl)-3-(benzoylmethyl)thio-
4H-1,2,4-triazole (3a). C17H16N4OS, m.wt. 324.4, pale
orange crystals, 68% yield, m.p. 129–30 °C (acetone).
Elemental analysis (%Calc./Found): 62.94/63.80 (C),
4.97/5.63 (H), 17.27/17.25 (N), 9.88/9.88% (S). IR (n,
cm−1): 3043, 2989 (ꢀCH aromatic); 2935, 2913 (CH
methylene, asimetric and simetric stretching); 1685
(CꢀO); 1598, 1565, 1478, 1390 (CꢀC and CꢀN of rings);
1435 (CH methylene bending); 826 (4-substituted pyri-
dine); 750, 695 (monosubstituted benzene); 641 (CꢁS).
1H NMR (l, ppm): 1.28 (3H, t, CH3), 4.13 (2H, q,
NCH2), 5.03 (2H, s, SCH2CO), 7.58 (2H, t, J=7.69
Hz, C3H and C5H of benzoyl), 7.69–7.72 (3H, m, C4H
of benzoyl and C3H, C5H of pyridine), 8.05 (2H, d,
C2H and C6H of benzoyl), 8.78 (2H, dd, J=6.12 Hz,
C2H and C6H of pyridine).
3.1.1.2. 4-(Phenethyl)-5-(4-pyridinyl)-2,4-dihydro-3H-
1,2,4-triazol-3-thione (2h). C15H14N4S, m.wt. 282.4,
colourless cubic crystals, 60% yield, m.p. 168 °C
(EtOH). Elemental analysis (%Calc./Found): 63.81/
64.53 (C), 5.00/5.51 (H), 19.84/19.84 (N), 11.35/11.35
(S). IR (n, cm−1): 3500–3350 (NH triazoline); 3043,
3000 (ꢀCH aromatic); 2825, 2828 (CH methylene, asi-
metric and simetric stretching); 1604, 1567, 1543, 1489,
1350 (CꢀC and CꢀN of rings); 1456 (CH methylene
bending); 1295 (CꢁN triazoline); 1261 (CꢀS); 826 (4-
1
substituted pyridine). H NMR, (l, ppm): 3.01 (2H, t,
CH2ꢁphenyl), 4.36 (2H, t, NCH2), 6.97–6.99 (2H, m,
C2H and C6H of phenyl), 7.18–7.22 (3H, m, C3H, C4H
and C5H of phenyl), 7.44 (2H, dd, J=5.99 Hz, C3H
and C5H of pyridine), 8.73 (2H, dd, J=5.98 Hz, C2H
and C6H of pyridine), 14.15 (1H, s, NH).
3.1.2.2. 4-Allyl-5-(4-pyridinyl)-3-(benzoylmethyl)thio-
4H-1,2,4-triazole (3b). C18H16N4OS·CH3OH, m.wt.
368.5, bright white powder, 70% yield, m.p. 75–77 °C
(methanol–water, 1:1). Elemental analysis (%Calc./
Found): 61.94/62.12 (C), 5.47/5.67 (H), 15.21/15.91 (N),
8.70/8.46% (S). IR (n, cm−1): 3475, 3370 (OH), 3043
(ꢀCH aromatic and allyl); 2967, 2913 (CH methylene,
asimetric and simetric stretching); 1685 (CꢀO); 1630,
1608, 1533, 1390 (CꢀC and CꢀN of rings, CꢀC of allyl);
3.1.2. General procedure for the preparation of 5-(4-
pyridinyl)-4-substituted-3-(benzoylmethyl)thio-4H-
1,2,4-triazoles (3a–g)
Equimolar amounts of 2a–g, phenacyl chloride and
dry potassium carbonate were refluxed in acetone (40
ml) for 8 h. The hot mixture was filtered. The precipi-

956
N.N. Gu¨lerman et al. / Il Farmaco 56 (2001) 953–958
1435 (CH methylene bending); 826 (4-substituted pyri-
dine); 760, 695 (monosubstituted benzene); 640 (CꢁS).
1H NMR (l, ppm): 4.78 (2H, NCH2), 4.89 (1H, d,
J=17.25 Hz, C3Ha of CHꢀCH2, trans), 5.01 (2H, s,
SCH2CO), 5.27 (1H, d, J=10.51 Hz, C3Hb of CHꢀCH2
cis), 5.90–6.14 (1H, m, CH), 7.59 (2H, t, J=7.69 Hz,
C3H and C5H of benzoyl), 7.66 (2H, dd, J=6.08 Hz,
C3H, C5H of pyridine), 7.71 (1H, t, J=7.40 Hz, C4H of
benzoyl), 8.04 (2H, d, J=8.51 Hz, C2H and C6H of
benzoyl), 8.76 (2H, dd, J=6.07 Hz, C2H and C6H of
62.98 (C), 3.72/4.13 (H), 13.77/14.01 (N), 7.78/7.29%
(S). IR (n, cm−1): 3054 (ꢀCH aromatic); 2967, 2913
(CH methylene, asimetric and simetric stretching); 1704
(CꢀO); 1591, 1489, 1369 (CꢀC and CꢀN of rings); 1438
(CH methylene bending); 1091 (ArꢁCl); 837 (1,4-disub-
stituted benzene and 4-substituted pyridine); 750, 695
(monosubstituted benzene); 630 (CꢁS). 1H NMR (l,
ppm): 4.98 (2H, s, CH2), 7.32 (2H, dd, J=6.15 Hz,
C3H and C5H of pyridine), 7.55–7.59 (4H, m, C3H and
C5H of benzoyl and phenyl), 7.67–7.72 (3H, m, C4H of
benzoyl and C2H and C6H of phenyl), 8.03 (2H, d,
J=8.50 Hz, C2H and C6H of benzoyl), 8.60 (2H, dd,
J=6.13 Hz, C2H and C6H of pyridine).
pyridine). MS m/z (%): 336 [M+] (0.17), 105
’
[phenylꢁCꢂO+] (100), 104 [pyridineꢁCꢂN]+ (13.5), 91
[phenylꢁCH2]+ (17), 77 [phenyl]+ (93).
3.1.2.3. 4-Phenyl-5-(4-pyridinyl)-3-(benzoylmethyl)thio-
4H-1,2,4-triazole (3c). C21H16N4OS, m.wt. 372.4,
creamy white powder, 31% yield, m.p. 175 °C (C3H6O).
Elemental analysis (%Calc./Found): 67.72/67.32 (C),
4.33/3.72 (H), 15.04/14.69 (N). IR (n, cm−1): 3054
(ꢀCH aromatic); 2978, 2913 (CH methylene, asimetric
and simetric stretching); 1674 (CꢀO); 1599, 1489,1369
(CꢀC and CꢀN of rings); 1435 (CH methylene bending);
826 (4-substituted pyridine); 761, 695 (monosubstituted
3.1.2.6. 4-(4-Fluorophenyl)-5-(4-pyridinyl)-3-(benzoyl-
methyl)thio-4H-1,2,4-triazole (3f). C21H15FN4OS, m.wt.
390.4, bright yellow crystals, 70% yield, m.p. 160–
161 °C (MeOH). Elemental analysis (%Calc./Found):
64.60/65.39 (C), 3.87/4.09 (H), 14.35/14.41 (N), 8.21/
8.25 (S). IR (n, cm−1): 3065 (ꢀCH aromatic); 2967,
2913 (CH methylene, asimetric and simetric stretching);
1700 (CꢀO); 1608, 1525, 1390 (CꢀC and CꢀN of rings);
1445 (CH methylene bending); 1175 (ArꢁF); 848 (1,4-
disubstituted benzene and 4-substituted pyridine); 750,
1
benzene); 630 (CꢁS). H NMR (l, ppm): 4.99 (2H, s,
1
CH2), 7.30 (2H, dd, J=6.05 Hz, C3H and C5H of
pyridine), 7.49–7.51 (2H, m, C2H and C6H of phenyl),
7.56–7.63 (5H, m, C3H, C4H and C5H of phenyl, C3H
and C5H of benzoyl), 7.70 (1H, t, J=7.36 Hz, C4H of
benzoyl), 8.04 (2H, d, J=7.38 Hz, C2H and C6H of
benzoyl), 8.57 (2H, dd, J=6.04 Hz, C2H and C6H of
pyridine).
695 (monosubstituted benzene); 640 (CꢁS). H NMR
(l, ppm): 4.81 (2H, s, CH2), 7.15 (2H, dd, J=6.13 Hz,
C3H and C5H of pyridine), 7.30 (2H, t, J=8.70 Hz,
C3H and C5H of phenyl), 7.38–7.44 (4H, m, C3H and
C5H of benzoyl and C2H and C6H of phenyl), 7.54 (1H,
t, J=7.37 Hz, C4H of benzoyl), 7.87 (2H, d, J=8.41
Hz, C2H and C6H of benzoyl), 8.43 (2H, dd, J=6.13
Hz, C2H and C6H of pyridine). MS m/z (%): 390 [M+]
3.1.2.4. 4-(4-Bromophenyl)-5-(4-pyridinyl)-3-(benzoyl-
methyl)thio-4H-1,2,4-triazole (3d). C21H15BrN4OS,
m.wt. 451.3, bright red crystals, 76% yield, m.p. 202 °C
(EtOH). Elemental analysis (%Calc./Found): 55.88/
55.92 (C), 3.35/2.96 (H), 12.41/12.43 (N), 7.10/6.79 (S).
IR (n, cm−1): 3087, 3043 (ꢀCH aromatic); 2974, 2913
(CH methylene, asimetric and simetric stretching); 1700
(CꢀO); 1610, 1500, 1390 (CꢀC and CꢀN of rings); 1435
(CH methylene bending); 1065 ( ArꢁBr); 826 (1,4-disub-
stituted benzene and 4-substituted pyridine); 760, 695
(monosubstituted benzene); 640 (CꢁS). 1H NMR (l,
ppm): 4.97 (2H, s, CH2), 7.32 (2H, dd, J=6.14 Hz,
C3H and C5H of pyridine), 7.49 (2H, dd, J=8.62 Hz,
C2H and C6H of phenyl), 7.58 (2H, t, J=7.71 Hz, C3H
and C5H of benzoyl), 7.70 (1H, t, J=7.39 Hz, C4H of
benzoyl), 7.82 (2H, dd, J=8.62 Hz, C3H and C5H of
phenyl), 8.03 (2H, d, J=8.50 Hz, C2H and C6H of
benzoyl), 8.60 (2H, dd, J=6.13 Hz, C2H and C6H of
pyridine).
(0.90), 105 [phenylꢁCꢂO]+ (95.1), 104 [pyri-
’
dineꢁCꢂN]+
(4.6), 95 [FꢁC6H5]+ (18.6), 91
[C6H5CH2]+ (14), 77 [phenyl]+ (100), 75 [95-HF] (19.9).
3.1.2.7. 4-Benzyl-5-(4-pyridinyl)-3-(benzoylmethyl)thio-
4H-1,2,4-triazole (3g). C22H18N4OS, m.wt. 386.5, white
crystals, 46% yield, m.p. 139 °C (C3H6O). Elemental
analysis (%Calc./Found): 68.37/69.51 (C), 4.69/4.44
(H), 14.50/14.70 (N). IR (n, cm−1): 3054 (ꢀCH aro-
matic); 2967, 2923 (CH methylene, asymmetric and
symmetric stretching); 1685 (CꢀO); 1587, 1454, 1348
(CꢀC and CꢀN of rings); 1425 (CH methylene bending);
826 (4-substituted pyridine); 735, 674 (monosubstituted
1
benzene); 641 (CꢁS). H NMR (l, ppm): 4.85 (2H, s,
SCH2CO), 5.26 (2H, s, NCH2), 6.88 (2H, d, J=6.92
Hz, C2H and C6H of benzyl), 7.10–7.19 (3H, m, C3H,
C4H and C5H of benzyl), 7.39–7.43 (4H, m, C3H and
C5H of benzoyl and pyridine), 7.54 (1H, t, J=7.39 Hz,
C4H of benzoyl), 7.87 (2H, d, J=7.16 Hz, C2H and
C6H of benzoyl), 8.52 (2H, dd, J=6.11 Hz, C2H and
3.1.2.5. 4-(4-Chlorophenyl)-5-(4-pyridinyl)-3-(benzoyl-
methyl)thio-4H-1,2,4-triazole (3e). C21H15ClN4OS,
m.wt. 406.9, orange crystals, 42% yield, m.p. 181 °C
(ethanol). Elemental analysis (%Calc./Found): 61.99/
C6H of pyridine). MS m/z (%): 386 [M+] (0.77), 105
’
[phenylꢁCꢂO]+ (90.6), 104 [pyridineꢁCꢂN]+ (11.5), 91
[C6H5CH2]+ (100), 77 [phenyl]+ (91), 65 [C5H5]+
(38.1).

N.N. Gu¨lerman et al. / Il Farmaco 56 (2001) 953–958
957
3.2. Microbiology
bacteria. Known antibacterial and antifungal antibi-
otics (cefotaxime and fluconazole, respectively) were
included to compare the results. DMSO which used in
dissolving of the compounds, had no effect on microor-
ganisms. The antimicrobial activity of the compounds
was tested on the Gram positive strains Bacillus subtilis
ATCC 6633, Staphylococcus aureus ATCC 6538P,
Staphylococcus epidermidis ATCC 12228, E. faecalis
ATCC 29212; the Gram negative strains Proteus
mirabilis ATCC 14153, Escherichia coli ATCC 8739,
Klebsiella pneumoniae ATCC 4352, Pseudomonas aerug-
inosa ATCC 27853, and the yeast strain C. albicans
ATCC 10231.
3.2.1. In 6itro e6aluation of antibacterial and antifungal
acti6ities
Tested compounds and control antibiotics were dis-
solved in DMSO and sterile distilled water, respectively
for the preparation of stock solutions. Further dilutions
were made in sterile distilled water. The in vitro antimi-
crobial activities of the tested compounds were carried
out by the paper disc diffusion method [17]. Overnight
cultures of microorganisms were adjusted to ca. 106
c.f.u. ml−1 according to the Mac Farland turbidity
standards [18] and spread over the appropriate media
(Mueller–Hinton agar for bacteria, same medium sup-
plemented with 5% blood for Enterococcus faecalis,
Sabouraud Dextrose Agar for the yeast), in petri dishes.
Filter paper discs (ƒ 5 mm) were placed on the surface
of the media and the solutions containing 500 mg of the
compounds were dropped on the discs. Discs contain-
ing DMSO were also used as control. After overnight
incubation at 37 °C, the zones of inhibition around the
discs were measured. The antimicrobial effects of the
compounds that produced ]12 mm zones of inhibition
were tested quantitatively in respective broth media by
using macrodilution method and the MIC (minimal
inhibitory concentration) values (mg ml−1) were deter-
mined [19]. The same test was carried out with DMSO
as control, as well as with the control antibiotics. For
candida albicans RPMI 1640 medium buffered with
MOPS was used for MIC determination [20].
As summarized in Table 1, compounds did not ex-
hibit activity against gram-positive and -negative bacte-
ria. The commonly used b-lactam antibiotic cefotaxime
was highly effective against B. subtilis, S. aureus, S.
epidermidis, E. faecalis, P. mirabilis, E. coli, K. pneumo-
niae and P. aeruginosa and its MIC values were 0.195,
1.56, 0.39, 156.2, 0.024, 0.097, 0.195 and 78.1 mg ml−1
,
respectively. The reference antifungal flucanozale was
highly active against C. albicans and its MIC value was
0.5 mg ml−1, while those of compounds 1c, 2a, 3a, 3c
and 3g were 50, 50, 25, 25 and 50 mg ml−1, respectively.
The MIC values for resistance are ]64, ]1 and
]32 mg ml−1 for commonly used antifungals flucona-
zole, itraconazole and flucytosine, respectively. The
value for intermediate activity for flucytosine is 8–16
mg ml−1 [20]. The antifungal activity of our compounds
3a and 3c fall between intermediate and resistant cate-
gory when compared with flucytosine. C. albicans
ATCC 10231 was not as resistant to compounds 1c, 2a,
3a, 3c and 3g as to fluconazole.
3.2.2. In 6itro e6aluation of antimycobacterial acti6ity
against Mycobacterium tuberculosis H37R6
According to primary antituberculosis activity re-
sults, the MIC values of compounds 2f, 2h and 3a–g
were higher than 6.25 mg ml−1, while the MIC value of
reference rifampicin was 0.25 mg ml−1. Compounds 2f,
3b–d showed low inhibition (2, 6, 12 and 16%, respec-
tively).
A primary screen was conducted at 6.25 mg ml−1 (or
molar equivalent of highest molecular weight com-
pound in a series of congeners) against M. tuberculosis
H37Rv in BACTEC 12B medium using a broth microdi-
lution assay, the Microplate Alamar Blue Assay
(MABA). Since their inhibitions were less than 90% in
the primary screen, compounds were not evaluated
further [21,22].
Acknowledgements
4. Results and discussion
We thank the Research Fund of Marmara University
which supported this work (project number SB-40/96)
and Dr Joseph A. Maddry from the Tuberculosis An-
timicrobial Acquisition and Coordinating Facility
Table 1 shows the antimicrobial activity of some of
the above mentioned compounds against a variety of
Table 1
Antibacterial activity of some of the compounds (MIC, mg ml−1
)
MIC
250
B. subtilis
S. aureus
S. epidermidis
1d, 1e, 2d, 2f
E. faecalis
P. mirabilis
1d, 1e, 2a
E. coli
K. pneumoniae P. aeruginosa
1a, 1c, 1d, 1f,
2a–d, 3b
1e, 2f, 3a
2f
1d, 2a, 2c, 2d,
2g, 2h, 3f
3b
1c, 1d, 1e, 2a,
3b
1c, 1d
2a, 2d
1c, 1d
500

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