Synthesis and antimicrobial activity of some novel quinoxalines

Article abstract of DOI:10.1080/00397911.2010.537802

2-Hydrazino-3-chloroquinoxaline 2 was prepared and reacted with active methylene compounds, potassium thiocyanate, carbon disulfide, phenylisothiocyanate, acetic acid, ethyl chloroformate, triethyl orthoformate, and Lawessen's reagent (LR) to give a new class of fused quinoxalines 4-16, respectively. Also, 2,3-dihydrazinoquinoxaline 3 was prepared and reacted with carbon disulfide, phenyl isothiocyanate, and triethyl orthoformate to give the corresponding di[1,2,4] triazolo-[4,3-a:3′,4′-c]-quinoxalines 17-19, respectively. Reaction of 3 with LR gave the corresponding di[1,2,4,3] triazophospholo[4,5-a:5′,4′-c]quinoxaline-1,6-dithione (20). It was found that all synthesized compounds exhibit antimicrobial activity and that compound 20 had a broad spectrum of activity. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.537802

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Synthesis and Antimicrobial Activity of
Some Novel Quinoxalines
A. M. Soliman a & A. A. Amer a
a Chemistry Department, Faculty of Science, Sohag, Egypt
Accepted author version posted online: 17 Nov 2011. Version of
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To cite this article: A. M. Soliman & A. A. Amer (2012): Synthesis and Antimicrobial Activity of Some
Novel Quinoxalines, Synthetic Communications: An International Journal for Rapid Communication of
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Synthetic Communications1, 42: 1401–1410, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.537802
SYNTHESIS AND ANTIMICROBIAL ACTIVITY
OF SOME NOVEL QUINOXALINES
A. M. Soliman and A. A. Amer
Chemistry Department, Faculty of Science, Sohag, Egypt
GRAPHICAL ABSTRACT
Abstract 2-Hydrazino-3-chloroquinoxaline 2 was prepared and reacted with active methyl-
ene compounds, potassium thiocyanate, carbon disulfide, phenylisothiocyanate, acetic acid,
ethyl chloroformate, triethyl orthoformate, and Lawessen’s reagent (LR) to give a new
class of fused quinoxalines 4–16, respectively. Also, 2,3-dihydrazinoquinoxaline 3 was pre-
pared and reacted with carbon disulfide, phenyl isothiocyanate, and triethyl orthoformate to
give the corresponding di[1,2,4] triazolo-[4,3-a:30,40-c]-quinoxalines 17–19, respectively.
Reaction of 3 with LR gave the corresponding di[1,2,4,3]triazophospholo[4,5-a:50,40-
c]quinoxaline-1,6-dithione (20). It was found that all synthesized compounds exhibit anti-
microbial activity and that compound 20 had a broad spectrum of activity.
Keywords Antimicrobial activity; polyfused; pyrazoles; quinoxalines; synthesis; triazoles
INTRODUCTION
Quinoxalines can act as glutamate receptors[1] or serine protease inhibitors,[1]
and have shown a broad spectrum of biological activities such as anticancer,[2]
antimicrobial,[2,3] antibacterial,[4,5] and antitumor[5] activities, which have made them
privileged structures in combinatorial drug discovery libraries.[6,7] Moreover, some
quinoxaline derivatives served as DNA photocleavers[8] and act as dyes.[9,10]
Furthermore, they act as useful rigid subunits in macrocyclic receptors for molecular
recognition[11,12] and chemically controllable switches.[13] Hence, they are an impor-
tant class of nitrogen-containing heterocycles and useful intermediates in organic
synthesis.[14]
In the light of these facts, we have synthesized some new families of fused and
polyfused heterocyclic compounds incorporating quinoxaline moiety with the hope
Received September 24, 2010.
Address correspondence to A. A. Amer, Chemistry Department, Faculty of Science, Sohag 82524,
Egypt. E-mail: Amer_chem@yahoo.com
1401

1402
A. M. SOLIMAN AND A. A. AMER
that they will possess better antimicrobial activity. All the synthesized compounds
were screened for their antibacterial and antifungal activities against some selected
microbes.
RESULTS AND DISCUSSIONS
Chemistry
The chemical synthesis commences with the preparation of 2-hydrazino-3-
chloroquinoxaline[15,16] (2) and 2,3-dihydrazinoquinoxaline[17] (3) by treating 2,3-
dichloroquinoxaline (1) with hydrazine hydrate in 1:1 or 1:2 molar ratios (Scheme 1).
Compound 2 was allowed to react with malononitrile in the presence of triethyl-
amine (TEA) as a basic catalyst to give the corresponding pyridazinoquinoxalin
derivative 4, while its reaction with other active methylene compounds (namely, ethyl
cyanoacetate or diethylmalonate) in the same reaction conditions furnished the pyr-
azoloquinoxaline derivatives 5 and 7, respectively. The expected fused products 6
and 8 were not obtained, perhaps because of the lesser reactivity of the methylene
group in these reagents than in the malononitrile. The formation of compound 4
was assumed to proceed via substitution of the chloro atom in compound 2 with
malononitrile to give the intermediate A followed by intermolecular cyclization
through nucleophilic attack of the NH2 group at CN group (Scheme 2). The first step
of the formation of compounds 5 and 7 was assumed to be the addition of an NH2
=
group of compound 1 at the C O group with elimination of ethanol molecule to
yield intermediates B and C, which then undergo intermolecular cyclization to give
the desired compounds 5 and 7 respectively.
Treatment of compound 2 with potassium thiocyanate in refluxing ethanol led
to the formation of quinoxaline derivative 9 and in turn refluxed in dimethyl forma-
mide (DMF) for 18 h to give the cyclized compound 10. Infrared (IR) spectrum of
compound 10 showed absorption peaks at 3395, 3320, and 3198 cmꢀ1, which corre-
1
spond to the presence of NH and NH2 groups, respectively, whereas its H NMR
showed a broad singlet signal at d 9.2 for the NH group, multiplet signals at
7.5–7.0 for the aromatic protons, and a broad signal at 5.2–4.6 for the NH2 group
(Scheme 2).
The biological activity of fused azoles has led to intensive research on their syn-
thesise.[18,19] Hence, in this work, we have tried to synthesize a new family of fused
Scheme 1. Reaction of 2,3-dichloroquinoxaline with hydrazine hydrate.

SYNTHESIS OF NOVEL QUINOXALINES
1403
Scheme 2. Reaction of compound 2 with some active methylene compounds.
s-triazoloquinoxaline via the reaction of compound 2 with different reagents, namely
carbon disulfide, phenyl isothiocyanate, acetic acid, ethylchloroformate, and triethyl
orthoformate, to give the corresponding triazoloquinoxaline derivatives 11–15,
respectively (Scheme 3). Treatment of compound 2 with Lawesson’s reagent (LR)
in boiling xylene gave 4-chloro-1-(4-methoxyphenyl)-1,2-dihydro[1,2,4,3]triaza-
phospholo-[4,5-a]quinoxaline-1-sulfide (16). The IR spectrum of compound 16 did
not show the band corresponding to the NH2 group, while exhibiting the character-
istic absorption band at 658 cmꢀ1 for P S. The H NMR spectrum of compound 16
1
=
exhibited a singlet signal at 3.7 ppm corresponding to the methoxy group. The mass
spectra of compound 16 showed a molecular ion at m=z 362 (83), consistent with for-
mation of the product (Scheme 3).
The o-dihydrazino function in compound 3 was exploited to synthesize some
new polyfused heterocyclic compounds. Compound 3 was reacted with carbon dis-
ulfide, phenyl isothicyanate, or triethyl orthoformate to give the corresponding
di[1,2,4]triazolo[4,3-a:30,40-c]quinoxalines derivatives 17–19, respectively. IR spectra
of compounds 17–19 showed the disappearance of the absorption bands correspond-
ing to the NH2 group. Compound 3 was allowed to react with LR in boiling xylene
to yield 1,6-bis(4-methoxyphenyl)-1,2,5,6-tetrahydrobis[1,2,4,3]triaza-phospholo-[4,5-
a:40,50-c]quino-xaline-1,6-disulfide 20 (Scheme 4).
The structures of new compounds were confirmed on the basis of elemental
analyses as well as spectral data.
Antimicrobial Evaluation
Newly synthesized compounds were screened for their antifungal activity
against Aspergillus flavus and Chrysosporium keratinophilum, and their antibacterial
activities were determined against Gram-positive bacteria (Staphylococcus aureus

1404
A. M. SOLIMAN AND A. A. AMER
Scheme 3. Synthesis of some new triazoloquinoxaline derivatives.
and Bacillus cereus) and Gram-negative bacteria (Pseudomonas aeruginosa and
Escherichia coli). The results of antimicrobial testing, as shown in Table 1, revealed
that compounds 4, 5, and 7 have little antimicrobial activity against either Gram-
positive and Gram-negative bacteria. Compounds 13 and 16 were comparable to
the standard against P. aeruginosa, while compound 16 was comparable to the stan-
dard against S. aureus.[20] Compounds 9–12 possessed little or no activity against
Gram-positive and Gram-negative bacteria. Compound 17 showed moderate
activity on Gram-negative bacteria, but it was more active on Gram-positive
bacteria. As for the antifungal activity, only compound 16 showed strong activity
against A. flavus, whereas compounds 4, 19, and 20 showed strong or very strong
Scheme 4. Synthesis of some new ditriazoloquinoxaline derivatives.

SYNTHESIS OF NOVEL QUINOXALINES
1405
Table 1. Antimicrobial activity of compounds 4–20 as indicated by their inhibition zone activity (mm)
Fungi
Gram-positive bacteria
Gram-negative bacteria
Comp.
A. flavus
C. keratinophilum
S. aureus
B. cereus
P. aeruginosa
E. coli
4
5
10
—
—
9
17
10
—
11
10
—
10
10
9
13
—
14
10
9
—
11
13
10
—
9
14
14
—
9
—
—
10
—
—
9
7
9
10
11
12
13
14
15
16
17
18
19
20
—
—
10
—
9
—
—
10
20
17
—
21
11
—
16
17
14
—
10
—
8
10
18
12
11
20
15
11
12
14
10
13
—
12
14
10
10
—
17
—
15
—
8
12
13
9
22
16
17
—
19
—
16
21
10
12
activities against C. keratinophilum. The other tested compounds showed weak or no
activity. Compound 20 can be considered as the most promising antibacterial and
antifungal agent (cf. Table 1).
CONCLUSIONS
In conclusion, several fused and polyfused quinoxalines 4–20 were synthesized.
Because of the availability of the starting materials, the simplicity of the procedures,
and the comparatively reasonable yields of the products, this synthetic approach
might be valuable for the synthesis of such ring systems. All the synthesized com-
pounds exhibited good antibacterial activity toward both Gram-positive and
Gram-negative bacteria. Some of the synthesized compounds showed good to mod-
erate activity against the tested fungi, especially C. keratinophilum, making these
compounds very important to treat this dermatophilic fungus.
EXPERIMENTAL
All melting points were determined on a Koffler melting-point apparatus and
are uncorrected. IR spectra were obtained on a Nicolet 710 Fourier transform
1
(FT)–IR spectrometer. H NMR spectra were recorded on a Varian EM 360 at
60 MHz using tetramethylsilane (TMS) as an internal reference and DMSO-d6 as
a solvent. Elemental analyses were performed on a Perkin-Elmer CHN-2400C ana-
lyzer model.
Methods of Synthesis
3-Amino-1,4-dihydropyridazino[3,4-b]quinoxaline-4-carbonitrile (4). An
equimolar ratio of compound 2 (1.94 g, 0.01 mol), malononitrile (0.66 g, 0.01 mol),

1406
A. M. SOLIMAN AND A. A. AMER
and triethylamine (TEA) (1.20 mL, 0.011 mol) was refluxed in ethanol (20 mL) for
5 h. After cooling, the reaction mixture was poured into ice-cold water containing
drops of HCl. The precipitated solid was filtered off, dried, and crystallized from
aqueous ethanol as brown crystals, 1.54 g (69%), mp 200 ꢁC; IR: 3555, 3344, 3214
(2NH, NH2); 2202 (CN) cmꢀ1; 1H NMR: 8.7 (br, s, 1H, NH), 7.8–6.9 (m, 4H, arom.,
1H, NH), 4.2–3.8 (br, 2H, NH2). Anal. calcd. for C11H8N6: C, 58.92; H, 3.60; N,
37.48. Found: C, 59.03; H, 3.44; N, 37.36.
1-(3-Chloroquinoxalin-2-yl)-1H-pyrazole-3,5-diol (5). An equimolar ratio
of compound 2 (1.94 g, 0.01 mol), diethylmalonate (1.50 mL, 0.01 mol), and TEA
(1.20 mL, 0.011 mol) was refluxed in ethanol (20 mL) for 7 h. After cooling, the reac-
tion mixture was poured into ice-cold water containing drops of HCl. The precipi-
tated solid was filtered, dried, and recrystallized from methanol as brown crystals,
1
1.34 g (51%), mp 294 ꢁC; IR: 3435 (OH) cmꢀ1; H NMR: 9.8 (br, s, 2H, 2OH),
7.8–6.9 (m, 4H, arom., 1H-pyrazole). Anal. calcd. for C11H7ClN4O2: C, 50.30; H,
2.69; N, 21.33. Found: C, 50.25; H, 2.48; N, 21.35.
5-Amino-1-(3-chloroquinoxalin-2-yl)-1,2-dihydro-3H-pyrazol-3-one (7).
An equimolar ratio of compound 2 (1.94 g, 0.01 mol), ethylcyanoacetate (1.07 mL,
0.01 mol), and TEA (1.20 mL, 0.011 mol) was refluxed in ethanol (20 mL) for 6 h.
After cooling, the reaction mixture was poured into ice-cold water containing drops
of HCl. The precipitated solid was filtered, dried, and recrystallized from dioxane as
red crystals, 1.54 g (68%), mp 143 ꢁC; IR: 3400 (NH), 3311, 3200 (NH2), 1673 (CO)
cmꢀ1; 1H NMR: d 8.1–7.0 (m, 4H, arom., 1H-pyrazole,1H, NH), 5.4–5.0 (br, s, 2H,
NH2). Anal. calcd. for C11H8ClN5O: C, 50.49; H,3.08; N, 26.76. Found: C, 50.50; H,
2.94; N, 26.80.
3-Hydrazinoquinoxalin-2-yl Thiocyanate (9). To an ethanol solution
(30 ml) of compound 2 (1.94 g, 0.01 mol), an equimolar amount of potassium thio-
cyanate (1.1 g, 0.011 mol) in water was added. After refluxuing for 10 min, a precipi-
tate was formed, which was filtered on hot and washed well with water to give a pure
reddish-brown powder, 1.7 g (78%), mp 300 ꢁC; IR 3421 (NH) 3294, 3201 (NH2),
1
2178 (SCN) cmꢀ1; H NMR: d 7.7–7.0 (m, 4H, arom., 1H, NH), 5.3–4.9 (br 2H,
NH2). Anal. calcd. for C9H7N5S: C, 49.76; H, 3.25; N, 32.24. Found: C, 49.73; H,
3.21; N, 32.26.
1H-[1,3,4]Thiadiazino[5,6-b]quinoxalin-3-amine (10). Compound 9 (1.5 g,
0.007 mol) was refluxed in dimethylformamide (DMF) for 18 h. The precipitated
product formed after cooling was filtered off and recrystallized from methanol as
brown crystals, 1.0 g (66.7%), charring at 320 ꢁC; IR 3395, 3320, 3198 (NH, NH2)
1
cmꢀ1; H NMR: d 9.2 (br, s, 1H, NH), 7.5–7.0 (m, 4H, arom.), 5.1–4.6 (br 2H,
NH2). Anal. calcd. for C9H7N5S: C, 49.76; H, 3.25; N, 32.24. Found: C, 49.73; H,
3.21; N, 32.26.
4-Chloro[1,2,4]triazolo[4,3-a]quinoxaline-1-thiol (11). A mixture of com-
pound 2 (1.94 g, 0.01 mol) and carbon disulphide (0.9 ml, 0,015 mol) in pyridine
(20 mL) was refluxed (until the evolution of H2S finished). The reaction mixture
was then poured onto cold water, and the solid product precipitated was collected
by filtration, dried, and recrystallized from dioxane as yellow crystals, 1.8 g (76%),

SYNTHESIS OF NOVEL QUINOXALINES
1407
1
mp 362 C; IR: 3112 (NH), 1154 (C S) cmꢀ1; H NMR: d 9.9 (br, s, NH), 7.4–6.9
(m, 4H, arom.). Anal. calcd. for C9H5ClN4S: C, 45.67; H, 2.13; N, 23.67. Found:
C, 45.64; H, 2.10; N, 23.70.
ꢁ
=
4-Chloro-N-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-1-amine (12). Com-
pound 2 (1.94 g, 0.01 mol) and phenyl isothiocyanate (1.25 mL, 0.01 mol) in pyridine
was allowed to reflux until the evolution of H2S finished. The reaction mixture was
cooled and diluted with water, and the resulting solid was recrystallized from ethanol
as yellow crystals, 2.4 g (81%), mp 176 ꢁC; IR: 3389 (NH) cmꢀ1; 1H NMR: d 9.7 (br,
s, 1H, NH), 7.5–6.7 (m, 9H, arom.). Anal. calcd. for C15H10ClN5: C, 60.92; H, 3.41;
N, 23.68. Found: C, 60.90; H, 3.39; N, 23.61.
4-Chloro-1-methyl[1,2,4]triazolo[4,3-a]quinoxaline (13). A mixture of
compound 2 (1.94 g, 0.01 mol) and acetic acid (10 mL) was heated under reflux for
4 h. After cooling, the precipitate was filtered and recrystallized from dioxane as a
1
yellow powder, 1.7 g (78%), mp 340 ꢁC; IR: 2910 (CH aliph.) cmꢀ1; H NMR: d
7.2–6.9 (m, 4H arom.), 2.3 (s, 3H, CH3). Anal. calcd. for C10H7ClN4: C, 54.93; H,
3.23; N, 25.62. Found: C, 55.08; H, 3.20; N, 25.65.
4-Chloro[1,2,4]triazolo[4,3-a]quinoxalin-1-ol (14). Compound 2 (1.94 g,
0.01 mol) and ethylchloroformate (3 mL) was allowed to reflux in pyridine (20 mL)
for 3 h. After cooling, the precipitated solid was filtered, washed well with water,
dried, and recrystallized from methanol as a dark brown powder, 1.2 g (54%), mp
1
355 ꢁC; IR: 3420 (OH) cmꢀ1; H NMR: d 9.2 (s, 1H, OH) 7.6–7.0 (m, 4H, arom.).
Anal. calcd. for C9H5ClN4O: C, 49.00; H, 2.28; N, 25.40. Found: C, 49.02; H,
2.25; N, 25.37.
4-Chloro[1,2,4]triazolo[4,3-a]quinoxaline (15). Compound
2
(1.94 g,
0.01 mol) was allowed to reflux in excess of triethyl orthoformate (15 mL) for 2 h
and left to cool to room temperature. The resulting precipitated solid was filtered,
dried, and recrystallized from ethanol as yellow crystals, 1.5 g (61%), mp 292 ꢁC; IR:
1613, (C N) cmꢀ1; 1H NMR: 8.5 (s, 1H, CH-triazole), d 8.0–7.5 (m, 4H, arom.). Anal.
=
calcd. for C9H5ClN4: C, 52.83; H, 2.46; N, 27.38. Found: C, 52.85; H, 2.43, N, 27.35.
4-Chloro-1-(4-methoxyphenyl)-1,2-dihydro[1,2,4,3]triazaphospholo-[4,5-
a]quinoxaline-1-sulfide (16). A mixture of 2,4-bis(4-methoxyphenyl)-1,3,2,4-
dithiadiphosphetane-2,4-disulfide (LR) (2.02 g, 0.005 mol) and compound 2 (1.94 g,
0.01 mole) in dry xylene (50 ml) was refluxed until no more of the reactants could
be detected by thin-layer chromatography (TLC) (5 h). The reaction mixture was
concentrated and left to cool to room temperature. The resultant precipitate was
collected by filtration and recrystallized from dioxane as a red powder, mp
215–217 C; IR: 3308 (NH), 658 (P S) cmꢀ1; H NMR: d 9.4 (br, s, 1H, NH),
1
ꢁ
=
7.6–7.0 (m, 8H, arom.) 3.7 (s, 3H, CH3). Anal. calcd. for C15H12ClN4OPS: C,
49.66; H, 3.33; N, 15.44. Found: C, 49.68; H, 3.31; N, 15.41.
Bis[1,2,4]triazolo[4,3-a:3’,4’-c]quinoxaline-3,10-dithiol (17). A mixture of
3 (1.90 g, 0.01 mol) and carbon disulfide (1.8 mL, 0.03 mol) in pyridine (20 mL) was
heated under reflux until the evolution of H2S finished. The reaction mixture was
then poured onto cold water, whereby the precipitated solid product was collected
by filtration, dried, and recrystallized from acetone as yellow crystals, 1.8 g (66%),

1408
A. M. SOLIMAN AND A. A. AMER
mp > 300 C; IR: 3216 (NH), 1146 (C S) cmꢀ1; 1H NMR: d 14.9 (s, 1H, SH), 10.5 (s,
1H, NH), 7.9–7.5 (m, 4H, arom.). Anal. calcd. for C10H6N6S2: C, 43.78; H, 2.20; N,
30.64. Found: C, 43.76; H, 2.18; N, 30.66.
ꢁ
=
N3, N10-Diphenylbis[1,2,4]triazolo[4,3-a:3’,4’-c]quinoxalin-3,10-diamine
(18). Compound
3 (1.90 g, 0.01 mol) and phenyl isothiocyanate (2.60 mL,
0.02 mol) in pyridine was allowed to reflux until the evolution of H2S finished.
The reaction mixture was cooled and diluted with water, and the resulting solid
was recrystallized from methanol as yellow powder, 2.1 g (54%), mp > 300 ꢁC; IR:
3230 (NH) cmꢀ1; 1H NMR: d 10.2 (br, s, 2H, 2NH), 7.7–6.8 (m, 14H, arom.). Anal.
calcd. for C22H16N8: C, 67.34; H, 4.11; N, 28.55. Found: C, 67.41; H, 4.08; N, 28.58.
Bis[1,2,4]triazolo[4,3-a:3’,4’-c]quinoxaline (19). Compound
3
(1.90 g,
0.01 mol) was allowed to reflux in excess of triethyl orthoformate (20 mL) for 5 h
and left to cool to room temperature. The resulting precipitated solid was filtered,
dried, and recrystallized from ethanol as a yellow powder, 1.6 g (76%), mp 321 ꢁC;
1
IR: 1631, (C N) cmꢀ1; H NMR: 8.3–7.4 (m, 4H, arom, 2H, 2CH, triazole). Anal.
calcd. for C10H6ClN6: C, 57.14; H, 2.88; N, 39.98. Found: C, 57.23; H, 2.73; N, 39.87.
=
1,6-Di(4-methoxyphenyl)-1,2,5,6-tetrahydrobis[1,2,4,5]triazaphospholo
[4,5-a:4’,5’-c]quinoxaline-1,6-disulfide (20). A mixture of 2,4-bis(4-methoxyphe-
nyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide LR (4.04 g, 0.01 mol) and compound 3
(1.90 g, 0.01 mol) in dry xylene (70 ml) was refluxed until no more of the reactants
could be detected (TLC) (7 h). The reaction mixture was concentrated and left to
cool to room temperature. The resultant precipitate was collected by filtration and
recrystallized from acetonitrile as-reddish-brown powder, 3.9 g (74%), mp 160 ꢁC;
1
IR: 3244 (NH), 661 (P S) cmꢀ1; H NMR: d 9.7 (br, s, 2H, 2NH), 7.7–7.0 (m,
=
12H, arom.), 3.88–3.85 (d, 6H, 2CH3). Anal. calcd. for C22H20N6O2P2S2: C, 50.19;
H, 3.83; N, 15.96; S, 12.18. Found: C, 50.21; H, 3.81; N, 15.99; S, 12.20.
Biological Method
The agar plate disc-diffusion method was applied.[21,22] Sterilized filter papers
(6 mm in diameter) were wetted with 10 mL of a solution of each compound to be
tested, containing 10 mg=mL in DMSO, and the discs were allowed to air dry.
The discs were then placed onto the surface of agar plates (nutrient agar for bacteria
and Sabouraud’s dextrose agar for fungi) seeded with the test organism. Each plate
contained 15 mL of the agar medium, previously seeded with 0.2 mL of the broth
culture of each organism pregrown for 18 h. The plates were incubated at 37 ꢁC
for 48 h for bacteria and 72 h for fungi. The inhibition zones was measured in milli-
meters. Discs impregnated with DMSO were used as a control, and its inhibition
zone was subtracted from the tested compound actual inhibition zone.
ACKNOWLEDGEMENT
We thank Dr. Yehia A.-G. Mahmoud, professor of Microbiology, Faculty of
Science, Tanta University, for his help and for providing the facilities during the
antimicrobial screening.

SYNTHESIS OF NOVEL QUINOXALINES
1409
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