Antimicrobial Activity of Amino Acid, Imidazole, and Sulfonamide Derivatives of Pyrazolo[3,4-d]pyrimidine

Article abstract of DOI:10.1002/hc.10212

Derivatives of pyrazolo[3,4-d]pyrimidine with amino acid 3a-d, imidazole 4a-d, carbonyl 6-9, pyrazole 10, pyrazolone 11, and sulfonamide 12-17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 12, and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b, 3c, 12, and 16 were nearly as active as Terbinafine as positive control.

Full text of DOI:10.1002/hc.10212

Heteroatom Chemistry
Volume 15, Number 1, 2004
Antimicrobial Activity of Amino Acid,
Imidazole, and Sulfonamide Derivatives
of Pyrazolo[3,4-d ]pyrimidine
M. M. Ghorab,1 Zeinab H. Ismail,2 Soad M. Abdel-Gawad,2
and Anhar Abdel Aziem2
1Department of Drug Radiation Research, National Centre for Radiation Research and Technology,
P.O. Box 29, Nasr City, Cairo, Egypt
2Department of Chemistry, Faculty of Science (Girl’s), Al-Azhar University, Cairo, Egypt
Received 19 May 2003; revised 17 July 2003
tion, sulfonamides have been widely used as bac-
ABSTRACT: Derivatives of pyrazolo[3,4-d]pyrimid-
teriostatic agents [8,9]. Having the above facts in
ine with amino acid 3a–d, imidazole 4a–d, carbonyl
mind and in continuation of our efforts to synthesize
6–9, pyrazole 10, pyrazolone 11, and sulfonamide
heterocyclic compounds containing pyrazolo[3,4-
12–17 moieties were synthesized. Structure of the new
d]pyrimidine [10], the present work was aimed at
compounds were established by their elemental analy-
new pyrazolo[3,4-d]pyrimidine derivatives expected
ses and spectral data. Some of the synthesized com-
to have antimicrobial activity.
pounds were tested in vitro for their antimicrobial
activity. Compounds 4b, 12, and 16 were almost as
potent as the standard antibiotic Chloramphenicol as
positive control. Also, compounds 3b, 3c, 12, and 16
Syntheses
When the chloro compound 1 [12] was allowed to
react with the sodium salt of various amino acids
under reflux at pH 9–9.5, the corresponding N-
(7-phenylpyrazolo[3,4-d]pyrimidin-4-yl)amino acids
3a–d were afforded (Scheme 1).
were nearly as active as Terbinafine as positive con-
ꢀ
C
trol.
2003 Wiley Periodicals, Inc. Heteroatom Chem
15:57–62, 2004; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10212
The structure of 3a–d were supported by elemen-
1
tal analyses, IR, H NMR, and mass spectral data.
INTRODUCTION
The structure of products showed ꢀNH and ꢀC O
in the 3400–3150 and 1720–1690 cm−1 regions re-
spectively, in addition to another band in the 1254–
1124 cm−1 region for a COOH group [13]. The IR
spectrum of 3a showed bands at 3398 (OH), 3220
(NH), 3101 (CH arom.), 1720 (C O), 1666, 1608
(2C N), 1230 cm−1 (CO2H). Its 1H NMR spectrum in
(DMSO-d6) exhibited signals at δ 4.2 [s, 2H, ꢁ-CH2],
7.2–7.6 [m, 5H, Ar H], 8.2 [s, 1H, NH], 8.4 [s, 1H,
CH pyrazole], 8.5 [s, 1H, CH pyrimidine], 8.8 [s, 1H,
OH]. The IR spectrum of 3b revealed bands at 3309–
2507 (OH), 3309 (NH), 3055 (CH arom.), 2931 (CH
A considerable number of pyrazolo[3,4-d]pyrimidi-
nes are known to be bioactive. They display an-
tibacterial [1], antifungal [2], antimicrobial [3],
antitumor [4], antiviral [5], and antipyretic [6] ac-
tivities. Compounds having amino acid moieties
are also known to possess a wide range of bio-
logical and pharmacological activity [7]. In addi-
Correspondence to: M. M. Ghorab; e-mail: ghorabmoustafa@
hotmail.com.
c
ꢀ
2003 Wiley Periodicals, Inc.
57

58 Ghorab et al.
(CH aliph.), 1697 (C O), 1651, 1596 cm−1 (C N).
The mass spectrum of 4b exhibited a molecular ion
peak m/z 265 (M+, 2.9%), with a base peak at 263;
other significant peaks appeared at 264 (M-1, 15.9%),
235 (13.5%), 221 (4.3%), 153 (4.5%), 132 (7.6%), 75
(1.9%). The IR spectrum of 4c showed bands at 3394
(OH), 3055 (CH arom.), 2931 (CH aliph.), 1751 cm−1
1
(C O). H NMR spectrum of 4c in (DMSO-d6) ex-
hibited signals at δ 1.2 [m, 2H, ꢃ-CH2], 2.3 [t, 1H,
ꢁ-CH], 7.3–7.8 [m, 5H, Ar H], 8.2, 8.4 [br, 2H, CH
pyrazole + CH pyrimidine], 8.5 (s, 1H, OH]. The IR
spectrum of 4d revealed bands at 2970 (CH aliph.),
1
1710 (C O) 1573 cm−1 (C N). H NMR spectrum
of 4d in (DMSO-d6) revealed bands at 0.9 [d, 6H,
2CH3], 5.2 (m, 1H, ꢃ-CH], 5.6 [d, 1H, ꢁ-CH], 7.2–8.0
[m, 5H, Ar H], 8.5, 8.6 [2s, 2H, CH pyrazole + CH
pyrimidine].
Compound 1 reacted with active methylene com-
pounds (malononitrile, ethyl cyanoacetate, acety-
lacetone, ethylacetoacetate, and diethylmalonate)
to afford the corresponding 4-alkylpyrazolo-
pyrimidine derivatives 5–9, respectively. The IR
spectrum of 5 showed bands at 3429 (NH), 2191
(C≡N), 1647 cm−1 (C N). The IR spectrum of 6
showed bands at 3200 (NH), 2221 (C≡N), 1712
(C O), 1643 cm−1 (C N). Its 1H NMR spectrum
in (DMSO-d6) showed signals at δ 1.3 [t, 3H, CH3
ethyl], 4.2 [q, 2H, CH2 ethyl], 7.4–8.1 [m, 5H, Ar H],
8.6, 8.7 [2s, 2H, CH pyrazole + CH pyrimidine], 11.5
[s, 1H, NH].
SCHEME 1
aliph.), 1710 (C O), 1666, 1620 (C N), 1242 cm−1
1
(CO2H). H NMR spectrum of 3b in (DMSO-d6) re-
vealed signals at δ 1.5 [d, 3H, CH3], 4.7 [q, 1H, ꢁ-
CH], 7.3–8.2 [m, 5H, Ar H], 8.4 [s, 1H, NH], 8.5 [s,
1H, CH pyrazole], 8.7 [s, 1H, CH pyrimidine], 8.8 [s,
1H, OH]. The IR spectrum of 3c exhibited bands at
3400–2507 (OH), 3224 (NH), 3062 (CH arom.), 2931
(CH aliph.), 1712 (C O), 1627 (C N), 1218 cm−1
(CO2H). The mass spectrum of 3c revealed a molec-
ular ion peak m/z 299 (M+, 7.1%), with a base peak
at 77; other significant peaks appeared at 281 (7.8%),
263 (36.8%), 236 (91.6%), 211 (61.5%), 195 (77.1%),
168 (31.6%), 141 (32.3%), 116 (19.6%), 51 (91.7%).
The IR spectrum of 3d showed bands at 3317 (OH),
3116 (NH), 3047 (CH arom.), 2962 (CH aliph.), 1674
(C O), 1596 (C N), 1218 cm−1 (CO2H). Its 1H NMR
spectrum (DMSO-d6) showed signals at δ 1.1 [d, 6H,
ꢂ-CH3], 2.3 [m, 1H, ꢃ-CH], 4.6 [t, 1H, ꢁ-CH], 7.3–8.0
[m, 5H, Ar H], 8.3, 8.4 [2s, 2H, CH pyrazole + CH
pyrimidine], 8.5 [d, 1H, NH], 8.7 [s, 1H, OH].
The IR spectrum of 7 showed bands at 3417
(NH), 3047 (CH arom.), 2923 (CH aliph.), 1735
(C O), 1596 cm−1 (C N). The IR spectrum of 8
showed bands at 3417 (NH), 3039 (CH arom.), 2930
1
(CH aliph.). The H NMR spectrum of 8 in (DMSO-
d6) revealed signals at δ 0.9 [t, 3H, CH3], 2.5 [s, 3H,
COCH3], 4.0 [q, 2H, CH2], 7.3–8.2 [m, 5H, Ar H],
8.3, 8.4 [2s, 2H, CH pyrazole + CH pyrimidine], 12.5
[s, 1H, NH]. The IR spectrum of 9 exhibited bands at
3163 (NH), 3047 (CH arom.), 2923 (CH aliph.), 1735
1
(C O), 1658 cm−1 (C N). Its H NMR spectrum in
(DMSO-d6) showed signals at δ 1.3 [t, 6H, 2CH3], 3.9
[q, 4H, 2CH2], 7.0–7.5 [m, 5H, Ar H], 8.0 (2s, 2H,
CH pyrazole + CH pyrimidine], 8.3 [s, 1H, NH].
It is reported that ꢃ-enaminonitriles reacted with
hydrazine to afford pyrazole derivatives [15]. Thus,
treatment of 5 and 6 with hydrazine hydrate in boil-
ing ethanol furnished the pyrazole 10 and pyra-
zolone 11 respectively (Scheme 2). The IR spec-
tra showed the disappearance (C≡N) and presence
(NH, NH2) of bands. The IR spectrum of 10 showed
bands at 3260, 3200 (NH, NH2), 3100 (CH arom.),
1600 cm−1 (C N). The mass spectrum of 10 exhib-
ited a molecular ion peak m/z 292 (M+, 1.72%), with
The amino acid derivatives 3a–d were then cy-
clized with acetic anhydride in the presence of an-
hydrous sodium acetate [14] to give the imidazol
derivatives 4a–d. Its IR spectra showed the absence
of (NH) band. The postulated structures were con-
firmed by IR, 1H NMR, and mass spectral data. The
IR spectrum of 4a showed bands at 2940 (CH aliph.),
1712 (C O), 1658 cm−1 (C N). H NMR spectrum
1
of 4a in (DMSO-d6) exhibited signals at δ 1.9 [s,
2H, CH2], 7.4–8.2 [m, 5H, Ar H], 8.6 [s, 1H, CH
pyrazole], 8.7 [s, 1H, CH pyrimidine]. The IR spec-
trum of 4b showed bands at 3101 (CH arom.), 2923

Antimicrobial Activity of Amino Acid, Imidazole, and Sulfonamide Derivatives of Pyrazolo[3,4-d ]pyrimidine 59
SCHEME 3
SCHEME 2
8.2 [2d, 4H, AB system], 8.6, 8.7 [2s, 2H, CH pyra-
a base peak at 211, and other significant peaks ap-
peared at 226 (3.1%), 183 (10.9%), 156 (10.3%), 129
(5.5%), 91 (8.4%), 77 (28.8%). The IR spectrum of
11 revealed bands at 3450, 3400, 3271 (NH, NH2),
3078 (CH arom.), 1674 (C O), 1596 cm−1 (C N). 1H
NMR spectrum of 11 in (DMSO-d6) exhibited sig-
nals at δ 7.2–7.8 [m, 7H, Ar H + NH2], 8.3, 8.5
[2s, 2H, CH pyrazole + CH pyrimidine), 9.2, 9.6
[2s, 2H, 2NH].
zole + CH pyrimidine], 10.6 [s, 1H, NHSO2], 11.5
[s, 1H, NH]. The IR spectrum of 15 showed bands
at 3340, 3217 (NH), 1627 cm−1 (C N). The IR spec-
trum of 16 showed bands at 3309, 3139 (NH), 3070
1
(CH arom.), 2923 (CH aliph.), 1635 cm−1 (C N). H
NMR spectrum of 16 in (DMSO-d6) revealed signals
at δ 2.2 [s, 6H, 2CH3], 6.8 [s, 1H, CH pyrimidine],
7.3–7.8 [m, 5H, Ar H], 7.9, 8.1 [2d, 4H, AB system],
8.6, 8.7 [2s, 2H, CH pyrazole + CH pyrimidine], 10.5
[s, 1H, NHSO2], 11.7 [s, 1H, NH]. The IR spectrum
of 17 showed bands at 3430, 3421 (NH, NH2), 1640
A literature survey revealed that because of their
biological activities sulfonamides have enormous
potential as pharmaceutical and agricultural agents.
They are associated with antibacterial [16], anti-
fungal [17], antitumor [18], and antiinflammatory
[19] properties. Condensation of 1 with some sul-
fonamides in N,N-dimethylformamide (DMF) gave
only the sulfonamide derivatives 12–16, whereas,
conducting this reaction in presence of anhydrous
K2CO3 [20] afforded sulfanilamide derivative 17
(Scheme 3). The IR spectrum of 12 showed bands
1
cm−1 (C N). H NMR spectrum of 17 in (DMSO-
d6) revealed signals at δ 6.6 [br, 2H, NH2], 7.2, 7.4
[2d, 4H, AB system], 7.8–8.4 [m, 5H, Ar H], 8.6,
8.7 [2s, 2H, CH pyrazole + CH pyrimidine], 10.6
[s, 1H, NHSO2]. The mass spectrum of 17 showed
a molecular ion peak m/z 366 (M+, 30.2%), with
a base peak at 77, and other significant peaks ap-
peared at 365 (M-1, 53.1%), 302 (2.0%), 286 (11.8%),
230 (2.9%), 182 (0.6%), 158 (3.6%), 90 (17.7%), 75
(17.1%).
1
at 3301, 3213 (NH, NH2), 1627 cm−1 (C N). Its H
NMR spectrum in (DMSO-d6) showed signals at δ
7.9–8.2 [2d, 4H, AB system], 7.3–8 [m, 5H, Ar H],
8.4 [s, 2H, NH2], 8.6, 8.7 [2s, 2H, CH pyrazole + CH
pyrimidine], 10.5 [s, 1H, NH]. The IR spectrum of 13
showed bands at 3433, 3332, 3217 (NH, NH2), 1627
(C O), 1581 cm−1 (C N). The mass spectrum of 13
showed a molecular ion peak m/z 408 (M+, 28.2%),
with a base peak at 365, and other significant peaks
appeared at 286 (26.6%), 211 (11.7%), 129 (12.4%),
75 (8.1%). The IR spectrum of 14 revealed bands at
EXPERIMENTAL
All melting points are uncorrected. Elemental analy-
ses were carried at the microanalytical laboratories
of the Faculty of Science, Cairo University. The IR
spectra (KBr) were measured on a Shimadzu IR 110
spectro-photometer. 1H NMR spectra were obtained
on a Bruker proton NMR-Avance 300 (300, MHz), in
DMSO-d6 as a solvent, using tetramethylsilane (TMS)
as internal standard. Mass spectra were run on HP
Model MS-5988.
1
3309, 3124 (2NH), 1627 cm−1 (C N). Its H NMR
spectrum exhibited signals at δ 2.3 [s, 3H, CH3], 6.2
[s, 1H, CH isoxazole], 7.3–7.8 [m, 5H, Ar H], 7.9,

60 Ghorab et al.
mixture. The separated solid was filtered off, washed
with water, and crystallized from ethanol to give 5
and 6 respectively (Table 1).
N-(7-Phenyl-pyrazolo[3,4-d]pyrimidin-4-yl)
amino Acids 3a–d
Amino acid (9.60 mmol) and sodium carbonate
(5.40 mmol) were dissolved in water (10 ml), then
adjusted to pH 9–9.5. The chloro derivative 1
(4.80 mmol) was then added and the mixture was
stirred at 100◦C for 6 h at controled pH. The reac-
tion mixture was left overnight at room temperature,
then treated with formic acid (88%). The solid prod-
uct obtained was filtered off, washed with water, and
crystallized from dioxane to give 3a–d (Table 1).
3-(1-Phenyl-1,5-dihydropyrazolo[3,4-d]-
pyrimidin-4-ylidene)pentane-2,4-dione 7,
3-Oxo-2-(1-phenyl-1,5-dihydropyrazolo-
[3,4-d]pyrimidin-4-ylidene)butyric Acid Ethyl
Ester 8, and 2-(Phenyl-1,5-dihydro-pyrazolo-
[3,4-d]pyrimidin-4-ylidene)malonic Acid Diethyl
Ester 9
Acetylacetone or ethyl acetoacetate and/or diethyl-
malonate (0.02 mol) was added to an ethanolic
sodium ethoxide solution (0.56 g of sodium in 50 ml
ethanol) and stirred for 2 h. The chloro derivative 1
(0.02 mol) was added and the reaction mixture was
heated under reflux on a water bath for 5 h. The
ethanol was removed under reduced pressure and
the residue was poured into 100 ml of cooled water
and extracted with chloroform. The extracted solvent
was dried over anhydrous magnesium sulphate and
removed under reduced pressure to afford 7, 8, and
9 respectively (Table 1).
2-Substituted 3-Oxo-7-phenylpyrazolo-
[2ꢁ,3ꢁ:4,5]pyrimido[6,1-c]imidazoles 4a–d
A mixture of 3a–d (10 mmol), acetic anhydride
(5 ml), and anhydrous sodium acetate (10 mmol)
was heated under reflux for 3 h. The solvent was re-
moved and the residue washed with water, filtered,
dried, and crystallized from DMF-EtOH to give 4a–d
(Table 1).
2-(1-Phenyl-1,5-dihydro-pyrazolo[3,4-d]-
pyrimidin-4-ylidene)malononitrile 5 and
Cyano-(1-phenyl-1,5-dihydro-pyrazolo[3,4-d]-
pyrimidin-4-ylidene)acetic Acid Ethyl Ester 6
4-(1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-
1H-pyrazole-3,5-diamine 10 and 5-Amino-4-
(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-
1,2-dihydro-pyrazol-3-one 11
A solution of 1 (10 mmol) and malononitrile or ethyl
cyanoacetate (10 mmol) in pyridine (20 ml) was re-
fluxed for 5 h, then cooled, and poured into ice/HCl
A mixture of 5, 6 (10 mmol), and hydrazine hydrate
(10 mmol) in ethanol (20 ml) was refluxed for 6 h,
TABLE 1 Physical and Analytical Data of the Synthesized Compounds
Required (Found) (%)
H
m.p. (◦C)
Yield (%)
Mol. Formula (Mol. Wt.)
C
N
3a
3b
3c
3d
4a
4b
4c
4d
5
223–225
174–176
205–207
115–117
278–280
250–252
335–337
337–239
>300
261–263
308–310
309–311
307–309
76–78
197–199
268–270
298–300
263–265
250–252
188–190
194–196
82
74
76
88
71
75
75
75
56
74
90
92
87
88
75
80
95
87
90
89
80
C13H11N5O (269)
57.99 (57.69)
59.36 (59.15)
56.18 (56.00)
61.73 (61.43)
62.15 (62.00)
63.39 (63.19)
59.78 (59.58)
65.52 (65.32)
64.61 (64.80)
62.54 (62.24)
65.30 (65.00)
62.96 (62.76)
61.01 (60.89)
57.53 (57.80)
57.33 (57.11)
55.73 (55.50)
52.94 (52.74)
56.37 (56.09)
50.00 (49.80)
58.47 (58.60)
55.73 (55.52)
4.08 (4.0)
26.02 (25.90)
24.73 (24.50)
23.41 (23.11)
22.50 (22.30)
27.88 (27.58)
26.41 (26.21)
24.91 (24.70)
23.89 (23.79)
32.30 (32.50)
22.80 (22.55)
19.04 (18.80)
17.28 (17.00)
15.81 (15.60)
38.35 (38.11)
33.44 (33.20)
22.95 (22.70)
27.45 (27.15)
21.92 (21.68)
23.33 (23.50)
23.72 (23.50)
22.95 (22.70)
C
C
C
C
C
C
C
14H13N5O2 (283)
4.59 (4.30)
4.34 (4.01)
5.46 (5.22)
3.58 (3.22)
4.15 (4.00)
3.91 (3.71)
5.11 (5.00)
3.07 (3.30)
4.23 (4.00)
4.76 (4.56)
4.93 (4.63)
5.08 (4.88)
4.10 (3.90)
3.75 (3.50)
3.82 (3.53)
3.92 (3.68)
3.80 (3.63)
3.33 (3.10)
4.23 (4.00)
3.82 (3.60)
14H13N5O2 (299)
16H17N5O3 (311)
2
13H9N5O (251)
14H11N5O (265)
14H11N5O (281)
16H15N5O2(293)
C14H8N6 (260)
6
C16H13N5O (307)
7
C16 14
H
N4O22 (294)
8
C
C
C
C
C
17H16N4O3 (324)
18H18N4O4 (354)
14H12N8 (292)
14H11N7O (293)
17H14N6O2S (366)
9
10
11
12
13
14
15
16
17
C18H16N8O2S (408)
C
C
C
C
21H17N7O S (447)
20H16N8O33S2 (480)
23H20N8O2S (472)
17H14N6O2S (366)

Antimicrobial Activity of Amino Acid, Imidazole, and Sulfonamide Derivatives of Pyrazolo[3,4-d ]pyrimidine 61
then allowed to cool. The solid product was collected
and crystallized from ethanol to give 10 and 11, re-
spectively (Table 1).
4-(1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-
4-ylamino)benzenesulfonamide Derivatives
12–16
A mixture of the chloro derivative 1 (10 mmol) and
sulfonamides (10 mmol) in N,N-dimethylformamide
(20 ml) was heated under reflux for 12 h and poured
into crushed ice. The solid product was collected and
crystallized from DMF-EtOH to give 12–16, respec-
tively (Table 1).
4-Amino-N-(1-phenyl-1H-pyrazolo[3,4-d]-
pyrimidin-4-yl)benzenesulfonamide
Sulfanilamide 17
A mixture of 1 (10 mmol), sulfanilamide (10 mmol),
and anhydrous K2CO3 (1 g) was refluxed in DMF
(30 ml) for 12 h, then cooled, and poured into
crushed ice. The solid product was collected and
crystallized from DMF/H2O to give 17 (Table 1).
ANTIMICROBIAL ACTIVITY
The antimicrobial screening of some synthesized
compounds was undertaken using the diffusion agar
technique [21]. Table 2 lists the screening results
of the tested compounds against the Gram-positive
bacteria Staphylococcus aureus and Bacillus subtilis,
the Gram-negative bacteria Pseudomonas aeruginosa
and Escherichia coli, and to the pathogenic fungi
Aspergillus fumigatus, Aspergillus flavus, Penicillium
species, and Candida albicans. The reference an-
tibiotic Chloramphenicol and fungicide Terbinafin
were used as positive controls for comparison. The
fungi cultures were maintained on Czapek’s Dox agar
medium. The tested compounds were dissolved in
N,N-dimethylformamide (DMF), which showed no
inhibition zones.
Pyrazolopyrimidine bearing imidazole 4b, pyra-
zolopyrimidine having benzenesulfonamide 12,
and pyrazolopyrimidine bearing N-(4,6-dimethyl-
pyrimidine) moiety 16 were found to be the most
active compounds against Gram-positive bacteria
S. aureus and B. subtilis. On the other hand,
pyrazolopyrimidine containing benzensulfonamide
12 and 16 showed high activity against Gram-
negative bacteria. In addition, pyrazolopyrimidine
having propionic acid 3b and benzenesulfonamide
12 and 16 exhibited good antifungal activity against

62 Ghorab et al.
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A. Eur J Med Chem 1998, 33, 83.
A. fumigatus, while compound 12 and 16 revealed re-
markable activity against A. flavus. Also, compounds
3b and 3c showed promising activity against Peni-
cillium species. Finally, compound 12 showed anti-
fungal activity against C. albicans. These results in-
dicated that the biologically active compounds 4b,
12, and 16 were almost as potent as the standard
antibiotic Chloramphenicol as positive control. Also
compounds, 3b, 3c, 12, and 16 were nearly as active
as Terbinafin as positive control.
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Many thanks are due to Prof. Dr. A. I. El-Batal,
Department of Drug Radiation Research, National
Centre for Radiation Research and Technology,
Cairo, Egypt, for doing the antimicrobial activity of
some synthesized compounds.
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