Synthesis, characterization and antimicrobial activity of new 1,2,3-selenadiazoles

Article abstract of DOI:10.3390/molecules13112740

The commercially available aromatic polyketones 1a-d were utilized for the synthesis of the multi-arm 1,2,3-selenadiazole derivatives 3a-d. The preparation starts with the reaction between compounds 1a-d and p-toluenesulfonyl hydrazide to give the corresponding tosylhydrazones 2a-d. Subsequent reaction with selenium dioxide leads to regiospecific ring closure of the tosylhydrazones to give the target multi-arm 1,2,3-selenadiazole derivatives in high yield. A 1,2,3-selenadiazole derivative 3e containing an epoxide ring was also prepared. The structures of all the synthesized compounds were confirmed on the basis of spectral and analytical data. The compounds were screened in vitro for their antimicrobial activity against various pathogenic bacterial and Candida strains obtained from King Abdullah Hospital in Irbid -Jordan. Compounds 3a, 3c and 3e were found to be highly active against all the selected pathogens. Compound 3e showed an inhibition zone of 13 mm against the highly resistant P. aruginosa.

Full text of DOI:10.3390/molecules13112740

Molecules 2008, 13, 2740-2749; DOI: 10.3390/molecules13112740
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis, Characterization and Antimicrobial Activity of New
1,2,3-Selenadiazoles
Mousa Al-Smadi 1,* and Fouad Al-Momani 2
1 Department of Applied Chemical Sciences, Jordan University of Science and Technology, P.O.Box
3030, Irbid 22110, Jordan
2 Department of Applied Biological Sciences, Jordan University of Science and Technology, P.O.Box
3030, Irbid 22110, Jordan
*Author to whom correspondence should be addressed; E-mail: mariam10@just.edu.jo.
Received: 5 June 2008; in revised form: 23 October 2008 / Accepted: 24 October 2008 / Published: 3
November 2008
Abstract: The commercially available aromatic polyketones 1a-d were utilized for the
synthesis of the multi-arm1,2,3-selenadiazole derivatives 3a-d. The preparation starts with
the reaction between compounds 1a-d and p-toluenesulfonyl hydrazide to give the
corresponding tosylhydrazones 2a-d. Subsequent reaction with selenium dioxide leads to
regiospecific ring closure of the tosylhydrazones to give the target multi-arm 1,2,3-
selenadiazole derivatives in high yield. A 1,2,3-selenadiazole derivative 3e containing an
epoxide ring was also prepared. The structures of all the synthesized compounds were
confirmed on the basis of spectral and analytical data. The compounds were screened in
vitro for their antimicrobial activity against various pathogenic bacterial and Candida
strains obtained from King Abdullah Hospital in Irbid -Jordan. Compounds 3a, 3c and 3e
were found to be highly active against all the selected pathogens. Compound 3e showed an
inhibition zone of 13 mm against the highly resistant P. aruginosa.
Keywords: Ketones; tosylhydrazones; 1,2,3-selenadiazoles; epoxide; antimicrobial
activity

Molecules 2008, 13
2741
Introduction
Selenium containing heterocyclic compounds are of interest due to their biological and synthetic
applications. 1,2,3-Selenadiazoles and derivatives are well known and have attracted attention as
versatile synthetic intermediates [1-2]. Many substituted 1,2,3-selenadiazoles and derivatives have
been prepared to-date and some of them show high antibacterial activity [3-6]. The antifungal activity
of other substituted 1,2,3-selenadiazoles has also been determined [6-8]. It has been found that the
introduction of a 1,2,3-selenadiazole ring to molecules of known biological activity compounds
changes their activities and in some cases leads to an increase in their biological activity [9]. Other
heterocyclic compounds containing five membered rings like triazole, oxazole, pyrazoline, pyrazole
and thiazole have been found to be biologically active substances [3, 11-12]. These ring systems are
present in numerous antiparasitic, fungicidal, antihelminitic and antiinflammatory drugs.
β-Lactam antibiotics derivatized with a 1,2,3-thiadiazole-5-mercapto moiety have been found to be
active against Gram-negative bacteria such as Pseudomonas aeruginosa. 4-Methyl-1,2,3-selena-
diazole-5-carboxamides have been described to inhibit tumor cell colony formation [13-14]. In the area
of antibacterial therapeutics, resistance to currently available drugs is progressively limiting their
utility in treating bacterial infections. This problem can be solved by discovering novel pharmaceutical
drugs that inhibit novel targets. Advances in molecular microbiology and genomics have led to the
identification of numerous bacterial genes that are encoding for novel proteins, that could potentially
serve as novel targets for antibacterial compounds. Regulatory proteins such as the two-component
histidine kinases, involved in bacterial signal transduction, have recently gained considerable attention
as one such class of potential targets [15].
As a continuation of our work on the synthesis of heterocyclic compounds containing 1,2,3-
thiadiazoles and 1,2,3-selenadiazoles [16-18], we have set out to synthesize a new group of
heterocyclic compounds containing 1,2,3-selenadiazole derivatives from the corresponding ketones
1a-d, respectively, hoping to obtain biologically active compounds with potential use in the
manufacture of pharmaceutical drugs. In this paper we present new data on the antimicrobial activities
of heterocyclic compounds containing 1,2,3-selenadiazole rings and the corresponding
tosylhydrazones.
Results and Discussion
The target 1,2,3-selenadiazole derivatives 3a-d were prepared from the corresponding tosyl-
hydrazones 2a-d as shown in Scheme 1. The synthetic procedure started from the commercially
available polyketones 1a-d. They were transformed into the target heterocyclic compounds by the
reaction of the tosylhydrazones with selenium dioxide, as previously described by Lalezari et. al. [19-
20]. Compound 3e was prepared by reaction of 4-(1,2,3-selenadiazole-4-yl)phenol [16] and
epichlorohydrin, as shown in Scheme 2.

Molecules 2008, 13
2742
Scheme 1.
O
S
H+
CH3
O
CH3
N
CH3
H2NNH-Tos
n
N
n
H
O
1a-d
SeO2
Dioxane
2a-d
N
Se
N
n
3a-d
Compound Position of Substitution
n
2
2
2
3
1-3a
1-3b
1-3c
1-3d
1,2-
1,3-
1,4-
1,3,5-
Scheme 2.
O
Se
K2CO3
KI, Acetone
OH
+
N
N
Cl
O
Se
2' 3'
O
N
1'
N
3e
The activity of these heterocyclic compounds and their tosylhydrazone precursors was tested
against some human pathogenic microbes including Gram-positive (Staphylococcus aureus), Gram-
negative (Escherichia coli, local resistant Pseudomonas aeruginosa and a reference Pseudomonas
aeruginosa ATCC 27853) and Candida albicans by two methods, namely by the hole diffusion (see
Table 1) and by the paper disk method (see Table 2).
From the results obtained from the two methods (Tables 1 and 2), it was found that some of the
tested heterocyclic compounds were highly active even at low concentrations (ie., at 0.005 g/mL or
less). Both methods indicated that the sensitivity of the highly resistance Pseudomonas. aeruginosa
and the sensitivity of a local, highly resistant clinical isolate, collected from King Abdullah Hospital at
Jordan University of Science and Technology, to some of these heterocyclic compounds is high.

Molecules 2008, 13
2743
The extracts of compounds 3a, 3c and 3e in dimethyl sulfoxide (DMSO) are active against all the
tested pathogens, with a (8-19 mm) inhibition zone diameter, when using the hole diffusion technique,
as indicated in Table 1. Pseudomonas. aeruginosa, a local isolate highly resistant to all domestic
antibiotics (amikacin, carbenicillin, cefoperazone, gentamicin, tobramycin), used in the clinical labs of
King Abdullah Hospital was found to be more sensitive to compound 3e. This isolate was also
sensitive to compounds 3a and 3c (at 0.01 g/mL) and to 3e (at 0.005 g/mL). The solvent showed no
activity against any of the tested pathogens.
Table 1. Sensitivity of human pathogenic microbes to the new synthetic heterocyclic
compounds using the hole method.
Pathogens
Conc.
Compound
Aa
B
C
D
E
(g/mL)
Tobramycin 0.010
15b
13
13
11
22
17
-
-
14
8
0.005
2a
2b
2c
2d
0.010
11
12
12
-
9
0.005
0.010
0.005
0.010
0.005
8
13
8
10
13
8
8
14
9
-
-
-
-
-
-
8
-
-
8
11
8
-
-
-
-
0.010
-
9
10
-
8
0.005
0.010
0.005
0.010
0.005
0.010
-
8
-
-
8
10
8
-
8
-
-
3a
3b
3c
12
9
14
10
15
12
14
9
-
11
10
8
11
8
-
-
8
10
8
0.005
0.010
0.005
0.010
0.005
-
-
-
9
8
-
-
10
8
3d
3e
-
-
-
-
-
-
13
13
13
-
19
14
10
9
15
9
a A: Staphylococcus aureus; B: Escherichia coli; C: Candida albicans; D: local
resistant Pseudomonas aeruginosa; E: reference Pseudomonas aeruginosa
ATCC 27853.
b Inhibition zone diameter measured in mm.

Molecules 2008, 13
Table 2. Sensitivity of human pathogenic microbes to the new synthetic heterocyclic
2744
compounds using the filter paper disk method.
Pathogens
C
Conc.
Compound
Aa
B
D
E
(g/mL)
Tobramycin 0.010
16b
10
14
12
24
16
-
-
16
10
0.005
2a
2b
2c
2d
0.010
10
13
14
-
9
0.005
0.010
0.005
0.010
0.005
8
13
9
10
14
10
9
8
15
9
-
-
-
-
-
-
8
-
-
13
9
9
-
-
-
0.010
0.005
0.010
0.005
0.010
0.005
0.010
8
-
9
-
9
-
-
-
9
-
3a
3b
3c
8
-
13
10
11
10
8
14
8
9
-
15
11
16
11
15
10
-
12
9
-
-
8
11
8
0.005
0.010
0.005
0.010
0.005
-
-
-
10
9
-
-
11
9
3d
3e
8
-
-
-
-
-
15
14
14
10
21
15
13
10
18
11
a A: Staphylococcus aureus; B: Escherichia coli; C: Candida albicans; D: local
resistant Pseudomonas aeruginosa; E: reference Pseudomonas aeruginosa
ATCC 27853.
b Inhibition zone diameter measured in mm.
As indicated from the present data, these synthetic heterocyclic compounds show potential as novel
antimicrobial agents, compared with the reference antibiotic tobramycin. Most of these heterocyclic
compounds are active against Candida albicans, a eukaryotic cell, so these synthetic heterocyclic
compounds should be studied further in the context of antitumor or anticancer drugs
(chemotherapeutic agents).
Acknowledgements
We are grateful to the Deanship of Scientific Research of the Jordan University of Science and
Technology for financial support. Also, we thank Prof. H. Meier from Mainz University-Germany for
helpful and worthy discussions.

Molecules 2008, 13
2745
Experimental
General
The melting points (m.p.) were determined on an Electro Thermal digital melting point apparatus. The
solvents were purified by standard procedures. Infrared (IR) spectra were recorded using a NICOLET
410 FT-IR spectrometer (in cm-1). The IR spectra of pure substances were measured as KBr-pellets.
NMR spectra were recorded on a Jeol JNM-ECP400 FT-NMR system at 400 MHz (1H-NMR) and 100
MHz (13C-NMR), respectively. The data are reported in delta (δ) units relative to tetramethylsilane
(TMS) used as internal reference. The mass spectra were measured on a Finnigan MAT95 instrument
(5 kV Ionizing energy, field desorption). The elemental analyses were performed in the analytical
laboratory of the Institute of Organic Chemistry of the University of Mainz, Germany. o-, m- and p-
Diacetylbenzene, and p-toluenesulfonyl hydrazide were obtained from Aldrich and 1,3,5-
triacetylbenzene, epichlorohydrin and dimethyl sulfoxide were obtained from Acros. Tobramycin was
obtained from Arcomex.
General procedure for the preparation of the tosylhydrazones 2a-d
A mixture of p-toluenesulfonyl hydrazide (0.60 mmol) and an equivalent amount of the appropriate
ketones (o-, m-, p-diacetylbenzene and 1,3,5-triacetylbenzene, 0.30 mmol and 0.20 mmol,
respectively) in absolute ethanol (35 mL) was refluxed for 1.5 hour. The reaction was followed by
TLC in chloroform until completion. The solution was cooled in an ice bath, concentrated to one third
of its original volume. The colorless solid product thus precipitated was filtered by vacuum filtration,
washed with several portions of cold ethanol and, when necessary, a recrystalization from ethanol was
performed.
(E,E)-1,1’-[1,2-Phenylene)bisethanone-bis(tosylhydrazone) (2a). Colorless powder, obtained in 73%
1
yield; m.p.147°C (decomposition); H-NMR (DMSO-d6): δ = 2.14 (s, 6H, CH3), 2.21 (s, 6H, CH3-
toluene), 7.33 (d, J = 7.6 Hz, 4H, toluene), 7.45 (d, J = 7.6 Hz, 4H, toluene), 7.57 (d, J = 7.4 Hz, 2H,
phenyl), 7.68 (d, J = 7.4 Hz, 2H, phenyl), 10.11 (s, 2H, NH) ppm; 13C-NMR (DMSO-d6): δ =
14.6/20.9 (4C, CH3), 123.8 (2C, CH-phenyl), 126.2 (2C, CH-phenyl), 128.4 (2C, CC-phenyl), 148.5
(2C, CN), 128.1 (4C, CH-toluene), 129.6 (4C, CH-toluene), 136.4 (2C, CC-Toluene), 142.7 (2C, CS-
toluene) ppm; IR (cm-1): ν = 3187, 1601, 1493, 1310, 1226, 921, 829; MS: m/z (%) 498 (100%); Anal.
Calcd. for C24H26N4O4S2: C, 57.81; H, 5.26; N, 11.24; S, 12.86. Found: C, 57.35; H, 5.56; N, 11.09.
(E,E)-1,1’-[1,3-Phenylene)bisethanone-bis(tosylhydrazone) (2b). Colorless powder, obtained in 82%
1
yield; m.p.163°C (decomposition); H-NMR (DMSO-d6): δ = 2.17 (s, 6H, CH3), 2.29 (s, 6H, CH3-
toluene), 7.37 (d, J = 7.6 Hz, 4H, toluene), 7.46 (d, J = 7.6 Hz, 4H, toluene), 7.53 (t, J = 7.4 Hz, 1H,
phenyl), 7.69 (d, J = 7.4 Hz, 2H, phenyl), 8.05 (s, 1H, phenyl), 10.14 (s, 2H, NH) ppm; 13C-NMR
(DMSO-d6): δ = 14.5/20.4 (4C, CH3), 123.8 (1C, CH-phenyl), 126.9 (2C, CH-phenyl), 128.6 (2C,
CC-phenyl), 138.3 (1C, CH-phenyl), 149.5 (2C, CN), 127.7 (4C, CH-toluene), 129.1 (4C, CH-
toluene), 136.3 (2C, CC-toluene), 142.9 (2C, CS-toluene) ppm; IR (cm-1): ν = 3193, 1591, 1501, 1312,

Molecules 2008, 13
2746
1232, 910, 828; MS: m/z (%) 498 (100%); Anal. Calcd. for C24H26N4O4S2: C, 57.81; H, 5.26; N, 11.24;
S, 12.86. Found: C, 57.42; H, 5.13; N, 11.13.
(E,E)-1,1’-[1,4-Phenylene)bisethanone-bis(tosylhydrazone) (2c). Colorless powder, obtained in 88%
1
yield; m.p.186°C (decomposition); H-NMR (DMSO-d6): δ = 2.20 (s, 6H, CH3), 2.32 (s, 6H, CH3-
toluene), 7.39 (d, J = 7.6 Hz, 4H, toluene), 7.48 (d, J = 7.6 Hz, 4H, toluene), 7.75 (s, 4H, phenyl),
13
10.17 (s, 2H, NH) ppm; C-NMR (DMSO-d6): δ = 14.3/20.7 (4C, CH3), 126.3 (4C, CH-phenyl),
129.6 (2C, CC-phenyl), 148.9 (2C, CN), 128.1 (4C, CH-toluene), 129.3 (4C, CH-toluene), 136.7 (2C,
CC-toluene), 143.1 (2C, CS-toluene) ppm; IR (cm-1): ν = 3213, 1591, 1521, 1312, 1246, 917, 826; MS:
m/z (%) 498 (100%); Anal. Calcd. for C24H26N4O4S2: C, 57.81; H, 5.26; N, 11.24; S, 12.86. Found: C,
57.53; H, 5.44; N, 11.42.
(E,E,E)-1,1’,1’’-[1,3,5-benzenetriyl)trisethanone-tris(tosylhydrazone) (2d). Colorless powder,
1
obtained in 84% yield; m.p.121°C (decomposition); H-NMR (DMSO-d6): δ = 2.23 (s, 9H, CH3),
2.35 (s, 9H, CH3-toluene), 7.41 (d, J = 7.6 Hz, 6H, toluene), 7.48 (d, J = 7.6 Hz, 6H, toluene), 8.01 (s,
13
3H, phenyl), 10.16 (s, 3H, NH) ppm; C-NMR (DMSO-d6): δ = 14.5/20.6 (6C, CH3), 124.4 (3C,
CH-phenyl), 138.2 (3C, CC-phenyl), 148.6 (3C, CN), 128.8 (6C, CH-toluene), 129.6 (6C, CH-
toluene), 136.5 (3C, CC-toluene), 142.7 (3C, CS-toluene) ppm; IR (cm-1): ν = 3189, 1587, 1584, 1506,
1321, 1243, 922, 825; MS: m/z (%) 708 (100%); Anal. Calcd. for C33H36N6O6S3: C, 55.92; H, 5.12; N,
11.86; S, 13.57. Found: C, 55.67; H, 5.24; N, 11.56.
General procedure for the preparation of the 1,2,3-selenadiazole derivatives 3a-d [16, 22]
Tosylhydrazone 2a-c or 2d (0.36 mmol) was mixed with an equivalent amount of selenium dioxide
powder (0.72 mmol) or (1.08 mmol), respectively, and sodium sulfate (3.0 g) in 1,4-dioxane (20 mL)
under vigorous stirring and gentle heating at 35-45°C. The solution was kept in the dark and the
reaction progress was monitored by TLC, showing that the reactions complete within about 20 hours.
After reducing in vacuo the volume of the reaction mixture to two thirds of its original volume,
distilled water (30 mL) was added, and the ensuing mixture was extracted with chloroform (3x20
mL).. The combined chloroform layers were dried over sodium sulphate. The crude product was
obtained after solvent removal in vacuo. Column chromatography using toluene/diethyl ether (7:3) as
eluent was used to separate the product, which can be recrystallized subsequently from
chloroform/hexane.
1,2-Bis(1,2,3-selenadiazole-4-yl)benzene (3a). Dark brown solid, obtained in 65% yield; m.p. 112°C
1
(decomposition); H-NMR (CDCl3): δ = 7.75 (d, J = 7.4 Hz, 2H, phenyl), 8.23 (d, J = 7.4 Hz, 2H,
13
phenyl), 8.97 (s, 2H, CHSe) ppm; C-NMR (CDCl3): δ = 124.7 (2C, CH-phenyl), 128.3 (2C, CH-
phenyl), 129.6 (2C, CC-phenyl), 133.2 (2C, C-Se), 162.3 (2C, C-N) ppm; IR (cm-1): ν = 3053, 1632,
1481, 1406, 1269, 1216, 957; MS: m/z (%) 340 (100%); Anal. Calcd. For C10H6N4Se2: C, 35.32; H,
1.78; N, 16.47; Se, 46.44. Found: C, 35.27; H, 1.75; N, 16.41.

Molecules 2008, 13
2747
1,3-Bis(1,2,3-selenadiazole-4-yl)benzene (3b). Dark brown solid, obtained in 72% yield; m.p. 133°C
1
(decomposition); H-NMR (CDCl3): δ = 7.69 (t, J = 7.4 Hz, 1H, phenyl), 8.15 (d, J = 7.4 Hz, 2H,
phenyl), 8.86 (s, 1H, phenyl), 8.93 (s, 2H, CHSe) ppm; 13C-NMR (CDCl3): δ = 121.3 (1C, CH-
phenyl), 124.3 (2C, CH-phenyl), 127.6 (1C, CH-phenyl), 130.1 (2C, CC-phenyl), 133.2 (2C, C-Se),
160.5 (2C, C-N) ppm; IR (cm-1): ν = 3060, 1628, 1476, 1419, 1253, 1225, 963; MS: m/z (%) 340
(100%); Anal. Calcd. For C10H6N4Se2: C, 35.32; H, 1.78; N, 16.47; Se, 46.44. Found: C, 35.27; H,
1.75; N, 16.41.
1,4-Bis(1,2,3-selenadiazole-4-yl)benzene (3c). Light brown solid, obtained in 78% yield; m.p. 122°C
1
(decomposition); H-NMR (CDCl3): δ = 8.16 (s, 4H, CH-phenyl), 8.69 (s, 2H, CHSe) ppm; 13C-
NMR (CDCl3): δ = 123.6 (4C, CH-phenyl), 129.4 (2C, CC-phenyl), 136.2 (2C, C-Se), 161.8 (2C, C-
N) ppm; IR (cm-1): ν = 3068, 1635, 1490, 1410, 1260, 1220, 960; MS: m/z (%) 340 (100%); Anal.
Calcd. For C10H6N4Se2: C, 35.32; H, 1.78; N, 16.47; Se, 46.44. Found: C, 35.29; H, 1.73; N, 16.43.
1,3,5-Tris(1,2,3-selenadiazole-4-yl)benzene (3d). Light brown solid, obtained in 81% yield; m.p.
131°C (decomposition); at 136°C the decomposed solid changed to a reddish brown liquid, while gas
1
13
evolution occurred; H-NMR (CDCl3): δ = 8.95 (s, 3H, CH-phenyl), 9.18 (s, 3H, CHSe) ppm; C-
NMR (CDCl3): δ = 122.9 (3C, CH-phenyl), 131.3 (3C, CC-phenyl), 138.8 (3C, C-Se), 162.1 (3C, C-N)
ppm; IR (cm-1): ν = 3086, 1598, 1496, 1414, 1223, 978; MS: m/z (%) 471 (100%); Anal. Calcd. For
C12H6N6Se3: C, 30.59; H, 1.28; N, 17.84; Se, 50.29. Found: C, 30.53; H, 1.25; N, 17.79.
3-[4-(1,2,3-Selenadiazole-4-yl)phenoxy]-1,2-propenoxide (3e)
This compound was obtained by reacting 4-(1,2,3-selenadiazole-4-yl)phenol (1.00 mmol) [20] with
epichlorohydrin (2.00 mmol), potassium carbonate (2.00 mmol) and potassium iodide (2.00 mmol) in
dry acetone (25 mL) under reflux. The reaction progress was followed by TLC (chloroform) showing
the completion of the reaction after 20 hours. Then water (25 mL) was added to the mixture. The
mixture was stirred for 5 min. and extracted with dichloromethane (3x15 mL). The organic phase was
dried over magnesium sulfate and concentrated to dryness. The residue was separated by column
chromatography on silica gel, using ethanol/dichloromethane (1:20) as eluant. The compound was
1
3
obtained as a light brown solid in 71% yield; m.p.163°C; H-NMR (CDCl3): δ = 2.65 (q, Jcis = 4.2
Hz, 1H, 3'-H), 2.94 (t, 3Jtrans = 2.3 Hz, 1H, 3'-H), 3.42 (m, 3Jcis = 4.5 Hz, 1H, 2'-H), 3.92 (q, 3Jtrans = 2.2
Hz, 1H, 1'-H), 4.26 (q, 3Jcis = 4.3 Hz, 1H, 1'-H), 7.11 (d, J = 7.4 Hz, 2H, CH-phenyl), 7.89 (d, J = 7.4
Hz, 2H, CH-phenyl), 9.08 (s, 1H, CHSe) ppm; 13C-NMR (CDCl3): δ = 44.7 (1C, CH2-epoxide), 50.8
(1C, CH-epoxide), 69.8 (1C, CH2O), 115.7 (2C, CH-phenyl), 125.7 (1C, CC-phenyl), 128.9 (2C, CH-
phenyl), 132.3 (1C, CHSe), 159.2 (1C, CO-phenyl), 162.2 (1C, CCSe) ppm; IR (cm-1): ν = 3088, 1602,
1523, 1462, 1253, 973; MS: m/z (%) 281 (100%); Anal. Calcd. For C11H10N2O2Se: C, 46.99; H, 3.56;
N, 9.96; Se, 28.08. Found: C, 46.93; H, 3.43; N, 9.89.

Molecules 2008, 13
2748
Microbiology
The filter paper disk and the hole diffusion methods were used to measure the inhibitory activity as
indicated by the diameter of the inhibition zone [21-22]. The filter paper disk method was carried out
as follows: Whatman III filter paper puncture disks 5 mm were saturated with different concentrations
of the heterocyclic compounds to be tested. They were dried in an oven at 60°C for 12 hours. The
dried disks were placed on already cultured nutrient agar plates concomitantly with the pathogens. The
diameter of the clear zone around the disks was measured after 48 hours of incubation at 37°C. The
absence of a clear zone around the disks indicated inactivity.
The hole method was carried out as follows: for each concentration, 100 µL of the heterocyclic
compounds were placed in 5 mm diameter wells on nutrient agar inoculated spontaneously with the
pathogens to be tested against. The plates were incubated at 37°C for 48 hours. The clear zone around
the wells was measured as inhibition zones. The absence of a clear zone around the well was taken as
inactivity. In both methods, DMSO was used as a solvent to prepare the solutions of the heterocyclic
compounds.
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diazoles. Angew. Chem. 1990, 102, 1450-1456.
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