Synthesis and antimicrobial evaluation of some new tetrahydropyrimidine derivatives

Article abstract of DOI:10.3987/COM-10-12104

The utility of 1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a,b), and 1,2-dihydropyrimidine-5-carboxylate (2) in the synthesis of some new functionalized pyrimidine derivatives such as 6-(2-(dimethylamino)vinyl)-1,2,3, 4- tetrahydropyrimidine, 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-1,2,3,4- tetrahydropyrimidine and 4,6-distyryl-1,2-dihydropyrimidine derivatives is reported. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed promising results. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-12104

HETEROCYCLES, Vol. 83, No. 3, 2011
609
HETEROCYCLES, Vol. 83, No. 3, 2011, pp. 609 - 617. © The Japan Institute of Heterocyclic Chemistry
Received, 18th November, 2010, Accepted, 6th January, 2011, Published online, 14th January, 2011
DOI: 10.3987/COM-10-12104
SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NEW
TETRAHYDROPYRIMIDINE DERIVATIVES
Yahia N. Mabkhot,1 Nabila A. Kheder,2,3,* and Ahmad M. Farag2
1Department of Chemistry, Faculty of Science, King Saud University, 2455,
2
Riyadh 11751, Saudi Arabia. Department of Chemistry, Faculty of Science,
Cairo University, Giza 12613, Egypt. 3On leave to Department of Pharmaceutical
Chemistry, Faculty of Pharmacy, King Khalid University, Abha, Saudi Arabia
*Corresponding author: E-mail: nabila_abdelshafy@yahoo.com
Abstract – The utility of 1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a,b), and
1,2-dihydropyrimidine-5-carboxylate (2) in the synthesis of some new
functionalized pyrimidine derivatives such as 6-(2-(dimethylamino)vinyl)-1,2,3,4-
tetrahydropyrimidine, 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-1,2,3,4-tetra-
hydropyrimidine and 4,6-distyryl-1,2-dihydropyrimidine derivatives is reported.
Antimicrobial evaluation of some selected examples from the synthesized
products was carried out and showed promising results.
Pyrimidine derivatives are reported to possess antibacterial,1-3 antifungal4,5 anticancer,6,7 anti-
inflammatory,8,9 and cardioprotective effects.10 In addition, certain pyrimidine derivatives are known to
display antimalarial, antifilarial and antileshmainal activities.11 Also, pyrimidine nucleus is considered as
one of the most important classes of chemotherapeutic drugs. Many pyrimidine derivatives are used for
thyroid drugs and leukemia.12 In view of the these results and as an extension of our recent work
concerned with the synthesis of heterocycles of interested biological activity13-20 we decided to synthesize
some
new
pyrimidine
derivatives
starting
from
the
readily
obtainable
1,2,3,4-
tetrahydropyrimidine-5-carboxylate derivatives 1a,21 1b,22 and dihydropyrimidine 223 as highly versatile
and useful building blocks for the synthesis of a wide variety of pyrimidine derivatives and to test their
antimicrobial activity.
1,2,3,4-Tetrahydropyrimidine 1a was found to react readily with dimethylformamide dimethyl acetal
(DMF-DMA) to produce ethyl 6-(2-(dimethylamino)vinyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-

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HETEROCYCLES, Vol. 83, No. 3, 2011
5-carboxylate (3) (Scheme 1). The IR spectrum of the product 3 showed absorption bands at, 1624, 1701,
1
3117, 3244 cm-1 due to two carbonyl groups, and two imino functions, respectively. Its H NMR
spectrum showed a triplet signal at  1.11 (J = 6.9 Hz) due to CH3 protons, singlet signal at  2.85,
characteristics for two methyl protons, a quartet signal at  3.96 (J = 6.9 Hz) due to CH2 protons, a
doublet signal at  5.17 (J = 3.6 Hz) due to CH proton, two doublets at  6.18 and  7.48 (J = 14.1 Hz)
due to two olefinic protons, and two D2O-exchangeable signals at  7.52 and 8.61 corresponding to two
NH protons, in addition to an aromatic multiplet in the region  7.22-7.29. The value of the coupling
constant for the ethylenic protons indicates that the pyrimidine 3 exists exclusively in the E-configuration.
Ph
Ph
OMe
EtO2C
NH
EtO2C
Me
MeO
-2MeOH
NH
N Me
+
N
O
Me
H
N
O
H
Me2N
3 (85%)
1a
(E)-configuration
Scheme 1
The versatile synthons; ethyl 6-(bromomethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (4a)24 and ethyl 6-(bromomethyl)-2-oxo-4-methyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (4b),24 were obtained from the bromination of ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (1a) and ethyl 4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (1b), in acetic acid. Attempted reaction of compound 4b with ethyl 3-oxo-3-
phenylpropanoate (5), in order to obtain the expected structure 7 or 8, was unsuccessful. Instead,
compound 4b underwent a thermal intramolecular cyclization reaction via elimination of bromoethane
and afforded the corresponding 4-methyl-3,4-dihydrofuro[3,4-d]pyrimidine-2,5(1H,7H)-dione (6)
(Scheme 2). Although ethyl 3-oxo-3-phenylpropanoate (5) is typically considered as a reagent, however,
it behaves as an adequate high boiling solvent in this thermal cyclization reaction.
The first step of this reaction is connected with a nucleophilic attack of the lone pair of electrons of
carbonyl oxygen in the ester group on the 6-bromomethyl group in 4b followed by thermal elimination of
bromoethane molecule under the reaction conditions to afford the final product 6. The latter product was
found to be identical in all respects [mp, mixed mp and IR spectrum] with that obtained from literature.24
Pyridinium N-ylides are highly interesting compounds due to their reactivity as organic dipoles as well as
their biological properties and applications. Usually, simple electron attracting groups, such as carbonyl,
cyano etc., have been used to delocalize the negative charge. Less attention has been paid to the
possibility of using heteroaryl groups as stabilizers except in the case of some tetrazole25 and triazole
stabilized ylides26 which already described. Our work in this field has been concerned with the synthesis

HETEROCYCLES, Vol. 83, No. 3, 2011
611
of pyrimid-6-yl stabilized pyridine ylide27 as a convenient root for producing highly stable dipole. Thus,
pyridinium bromides 9a and 9b were prepared from 4a or 4b with an equivalent amount of pyridine in
dry THF (Scheme 3).
Et
O
Me
O
O
O
NH
+
EtO
Ph
N
H
4b
O
5
Br
- EtBr
1. -HBr
2. - EtOH
1. -HBr
2. - EtOH
Me
Me
NH
Me
O
O
EtO2C
NH
EtO2C
Ph
NH
O
N
O
N
H
O
N
O
H
O
O
O
6 (70%)
7
Ph
8
Scheme 2
Reaction of the ethyl 6-(bromomethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a)
with potassium cyanide afforded the corresponding pyrimidine derivative 10.28
Y
EtO2C
NH
N
N
O
Br
4a,b
H
N
4,9: a
, Y= Ph
9a (88%)
9b (83%)
b, Y= Me
Scheme 3
Treatment of the latter compound with phenyl isothiocyanate, in N,N-dimethylformamide, and in the
presence of potassium hydroxide, at room temperature, followed by treatment with dilute hydrochloric
acid, afforded the corresponding ethyl 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-2-oxo-4-phenyl-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (12) (Scheme 4).
Treatment of ethyl 4,6-dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylate (2) with the appropriate
aromatic aldehydes in the presence of a catalytic amount of ZnCl2, afforded the corresponding bis-
arylidene derivatives 13a-c (Scheme 5). The above reaction is assumed to proceed via loss of two water
molecules.

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HETEROCYCLES, Vol. 83, No. 3, 2011
Ph
Ph
Ph
EtO2C
NC
EtO2C
PhNCS
DMF
EtO2C
NH
NH
dil HCl
NH
NC
N
H
O
N
O
N
H
O
H
PhHN
S
CN
PhHN
SK
10
12 (62%)
11
Scheme 4
The Structure of the isolated products was assigned as ethyl 4,6-bis(substituted)-2-oxo-1,2-
dihydropyrimidine-5-carboxylate 13a-c based on their elemental analyses and their spectroscopic data.
The 1H NMR spectrum spectra of the isolated products showed in each case the absence of methyl signal
and the value of the coupling constant for the ethylenic protons indicates that the pyrimidine 13 exists
exclusively in the E-configuration.
Ar
Me
EtO2C
Me
-2H2O
EtO2C
Ar
N
N
2 ArCHO
N
H
2
O
N
H
O
13
13:
Ar, a = Ph (70%)
(E)-configuration
b = 4-MeOPh (74%)
c = 4-ClPh (76%)
Scheme 5
In conclusion, the utility 1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a,b), and 1,2-dihydropyrimidine-
5-carboxylate (2) in the synthesis of some new functionalized pyrimidine derivatives of biological and
pharmaceutical importance is reported.
EXPERIMENTAL
All melting points were measured on a Gallenkamp melting point apparatus. The infrared spectra were
recorded in potassium bromide disks on a pye Unicam SP 3300 and Shimadzu FT IR 8101 PC infrared
spectrophotometers. The NMR spectra were recorded on a Varian Mercury VX-300 NMR spectrometer.
1H spectra were run at 300 MHz and 13C spectra were run at 75.46 MHz in dimethyl sulphoxide
(DMSO-d6). Chemical shifts were related to that of the solvent. Mass spectra were recorded on a
Shimadzu GCMS-QP 1000 EX mass spectrometer at 70 e.V. Elemental analyses (C, H, N, S) were
carried out at the Microanalytical Center of Cairo University, Giza, Egypt. The biological evaluation of
the products 9b, 12, 13a and 13c were carried out in the Medical Mycology Laboratory of the Regional
Center for Mycology and Biotechnology of Al-Azhar University, Cairo, Egypt. Ethyl
6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a),21 ethyl 4,6-dimethyl-2-oxo-

HETEROCYCLES, Vol. 83, No. 3, 2011
613
1,2,3,4-tetrahydropyrimidine-5-carboxylate (1b),22 ethyl 4,6-dimethyl-2-oxo-1,2-dihydropyrimidine-5-
carboxylate (2),23 ethyl 6-(bromomethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4a),24 ethyl 6-(bromometh-yl)-2-oxo-4-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4b)24 and
ethyl 6-(cyanomethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (10)28 were prepared
following the literature procedure.
Ethyl 6-(2-(dimethylamino)vinyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3).
A mixture of compound 1 (2.60 g, 10 mmol) and dimethylformamide dimethyl acetal (DMF-DMA) (1.33
mL, 10 mmol) in dry xylene (20 mL) was refluxed for 3 h, then left to cool. The precipitated product was
filtered off, washed with EtOH and dried. Recrystallization from dioxane/ EtOH gave yellow crystals of
compound 3 in 85% yield, mp 244-245 oC; IR (KBr) v 3244 (NH), 3117 (NH), 1701 (C=O), 1624 (C=O)
cm-1; 1H NMR (DMSO-d6) δ 1.11 (t, 3H, CH3, J = 6.9 Hz), 2.85 (s, 6H, 2NCH3), 3.96 (q, 2H, CH2, J = 6.9
Hz), 5.17 (d, 1H, J = 3.6 Hz), 6.18 (d, 1H, CH, J= 14.1 Hz), 7.22-7.29 (m, 5H), 7.48 (d,1H, CH, J= 14.1
Hz), 7.52 (s, 1H, D2O-exchangeable NH), 8.61 (s, 1H, D2O-exchangeable NH); MS m/z (%) 315 (M+,
20.0), 238 (100), 77 (36.0). Anal. Calcd for C17H21N3O3: C, 64.74; H, 6.71; N, 13.32. Found: C, 64.80; H,
6.67; N, 13.26%.
Attempted reaction of 6-bromomethylpyrimidine 4b with ethyl 3-oxo-3-phenylpropanoate (5).
To an ethanolic solution of 6-bromomethylpyrimidine 4b (0.28 g, 1 mmol) and ethyl 3-oxo-3-phenyl-
propanoate (5) (0.19 mL, 1 mmol) was added few drops of piperidine and the reaction mixture was
refluxed for 4 h. The formed solid product was collected by filtration, washed with EtOH and purified by
crystallisation
from
the
DMF
to
afford
a
product
identified
as
4-methyl-3,4-dihydrofuro[3,4-d]pyrimidine- 2,5(1H,7H)-dione (6): Yield (70%), mp 268 °C. The latter
product is assumed to be formed through an intramolecular cyclization of compound 4b via thermal
elimination of bromoethane and it was found to be identical in all respects (mp, mixed mp and IR
spectrum) with an authentic sample prepared according to a literature procedure.24 It is noteworthy that
ethyl 3-oxo-3-phenylpropanoate (5) was not involved in above reaction but it acted as a suitable high
boiling solvent for the above reaction. IR (KBr) v 3310 (NH), 3228 (NH), 1726 (C=O), 1662 (C=O)
cm-1; 1H NMR (DMSO-d6)  1.24 (s, 3H, CH3), 4.27 (d, 1H, CH, J = 5.1 Hz), 4.74 (s, 2H, CH2), 7.3 (s,
1H, D2O-exchangeable NH), 9.68 (s, 1H, D2O-exchangeable NH). Anal. Calcd for C7H8N2O3: C, 50.00;
H, 4.80; N, 16.66. Found: C, 50.12; H, 4.88; N, 16.64%.
Reaction of 6-bromomethylpyrimidine 4a or 4b with pyridine.
To a solution of 6-bromomethylpyrimidine 4a or 4b (10 mmol) in dry THF (20 mL), pyridine (0.8 mL, 10
mmol) was added. The reaction mixture was refluxed for 20 min, then left to cool to rt. The solid product
was filtered off, washed with Et2O and dried to afford the corresponding pyridinium salts 9a and 9b,
respectively.

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HETEROCYCLES, Vol. 83, No. 3, 2011
1-[(5-(Ethoxycarbonyl)-2-oxo-6-phenyl-1,2,3,6-tetrahydropyrimidin-4-yl)methyl]pyridiniumbromide
1
(9a): Yield (88%), mp 197 ºC; IR (KBr) v 3230 (NH), 3093 (NH), 1700 (C=O), 1647 (C=O) cm-1; H
NMR (DMSO-d6)  1.09 (t, 3H, CH3, J = 6.9 Hz), 3.97 (q, 2H, CH2, J = 6.9 Hz), 4.82 (s, 2H, CH2), 5.14
(s, 1H), 7.22-7.35 (m, 10H, Ar-H), 7.70 (s, br., 1H, D2O-exchangeable NH), 9.15 (s, br., 1H,
D2O-exchangeable NH). Anal. Calcd for C19H20BrO3N3: C, 54.56; H, 4.82; N, 10.05. Found: C, 54.62; H,
4.89; N, 10.12%.
1-[(5-(Ethoxycarbonyl)-6-methyl-2-oxo-1,2,3,6-tetrahydropyrimidin-4-yl)methyl]pyridiniumbromide
1
(9b): Yield (83%), mp 220 ºC; IR (KBr) v 3283 (NH), 3202 (NH), 1701 (C=O), 1659 (C=O) cm-1; H
NMR (DMSO-d6)  1.18 (t, 3H, CH3, J = 6.9 Hz), 1.22 (s, 3H, CH3), 4.12 (q, 2H, CH2, J = 6.9 Hz), 4.24
(s, 2H, CH2), 5.58 (s, 1H) , 7.48 (s, br., 1H, D2O-exchangeable NH), 8.17 (m, 2H), 8.64 (m, 1 H), 9.0 (d,
2H), 9.52 (s, br., 1H, D2O-exchangeable NH). Anal. Calcd for C14H18BrO3N3: C, 47.20; H, 5.09; N, 11.80.
Found: C, 47.29; H, 5.02; N, 11.88%.
Ethyl 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (12).
To a stirred solution of potassium hydroxide (0.11 g, 2 mmol) in DMF (20 mL) was added the pyrimidine
derivative 1028 (0. 57 g, 2 mmol). After stirring for 30 min, phenyl isothiocyanate (0.27 g, 2 mmol) was
added to the resulting mixture. Stirring was continued for 6 h, and then the reaction mixture was poured
over a cold solution of 0.5 N hydrochloric acid. The formed solid product was filtered off, washed with
water, dried, and finally recrystallized from the EtOH to afford compound 12 in 62% yield, mp 175 ºC; IR
(KBr) v 3209 (NH), 3101 (NH), 3051 (NH), 1697 (C=O), 1632 (C=O) cm-1; 1H NMR (DMSO-d6)  1.1 (t,
3H, CH3, J = 6.9 Hz), 4.06 (q, 2H, CH2, J = 6.9 Hz), 4.13 (s, 1H), 5.18 (d, 1H, CH, J = 2.4 Hz), 7.22-7.37
(m, 10H, Ar-H), 7.91 (s, br., 1H, D2O-exchangeable NH), 8.0 (s, br., 1H, D2O-exchangeable NH), 9.71 (s,
1H, D2O-exchangeable, NH); MS m/z (%) 420 (M+, 5.2), 419 (7.9), 374 (2.5), 373 (6.4), 339 (100.0),
291(13.7), 257 (60.7), 185 (52.8), 77 (85.2). Anal. Calcd for C22H20N4O3S: C, 62.84; H, 4.79; N, 13.32%.
Found: C, 62.80; H, 4.84; N, 13.28%.
Reaction of ethyl 4,6-dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylate (2) with aromatic aldehydes
General procedure:
A mixture of the appropriate aromatic aldehyde (20 mmol), the pyrimidine derivative 2 (1.96 g, 10 mmol)
and zinc chloride (1 mmol) was heated at 100 º C with constant stirring for 1 h. After all starting material
was consumed (TLC), the solution was cooled to ambient temperature. The precipitated crude product
was purified by recrystallization from EtOH / DMF to afford the corresponding bis-arylidene derivative
13a-c.
Ethyl 2-oxo-4,6-distyryl-1,2-dihydropyrimidine-5-carboxylate (13a): Yield (70%), mp 213 ºC; IR (KBr):

HETEROCYCLES, Vol. 83, No. 3, 2011
615
1623 (C=O), 1711 (C=O), 3024 (NH) cm-1; 1H NMR (DMSO-d6)  1.28 (t, 3H, CH3, J = 7.2 Hz), 4.57 (q,
2H, CH2, J = 7.2 Hz), 6.95 (d, 2H, J = 15.85 Hz), 7.45-7.61 (m, 10H), 7.83 (d, 2H, J = 15.85 Hz), 12.10
(s, br., 1H, D2O-exchangeable NH); MS m/z (%) 373 (16.7), 372 (M+, 44.2), 371 (54.3), 343 (100.0), 299
(73.2), 254 (12.3), 130 (16.0), 77 (24.2). Anal. Calcd for C23H20N2O3: C, 74.18; H, 5.41; N, 7.52%.
Found: C, 74.10; H, 5.35; N, 7.56%.
Ethyl 4,6-bis(4-methoxystyryl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate (13b): Yield (74%), mp 220
1
ºC; IR (KBr): 1628 (C=O), 1712 (C=O), 3202 (NH) cm-1; H NMR (DMSO-d6)  1.33 (t, 3H, CH3, J =
7.2 Hz), 3.81 (s, 6H, OCH3), 4.45 (q, 2H, CH2, J = 7.2 Hz), 7.0-7.05 (m, 6H), 7.60 (d, 4H, J = 8.7 Hz),
7.85 (d, 2H, J = 15.9 Hz), 11.9 (s, br., 1H, D2O-exchangeable NH); MS m/z (%) 432 (M+, 30.4), 403
(100.0), 359 (26.8), 315 (14.3), 285 (39.3), 121 (51.8), 77 (57.1). Anal. Calcd for C25H24N2O5: C, 69.43;
H, 5.59; N, 6.48%. Found: C, 69.49; H, 5.50; N, 6.56%.
Ethyl 4,6-bis(4-chlorostyryl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate (13c): Yield (76%), mp > 300
1
ºC; IR (KBr): 1628 (C=O), 1709 (C=O), 3098 (NH) cm-1; H NMR (DMSO-d6)  1.29 (t, 3H, CH3, J =
7.2 Hz), 4.41 (q, 2H, CH2, J = 7.2 Hz), 7.27 (d, 2H, J = 15.9 Hz), 7.43-7.6 (m, 11H, Ar-H+NH); MS m/z
(%) 368 (10.0), 367 (M+ -EtOCO, 60.0), 174 (30.0), 127 (45.0), 86 (35.0). Anal. Calcd for
C23H18Cl2N2O3: C, 62.60; H, 4.11; N, 6.35 %. Found: C, 62.67; H, 4.04; N, 6.30%.
ANTIMICROBIAL EVALUATION
Four of the newly synthesized target compounds were evaluated for their in vitro antibacterial activity
against Staphylococcus aureus (RCMB 000106) and Bacillis subtilis (RCMB 000107) as examples of
Gram-positive bacteria and Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB
000103) as examples of Gram-negative bacteria. They were also evaluated for their in vitro antifungal
potential against Aspergillus fumigatus (RCMB 002003), Geotrichum candidum (RCMB 052006),
Candida albicans (RCMB 005002) and Syncephalastrum racemosum (RCMB 005003) fungal strains.
Agar-diffusion method was used for the determination of the antibacterial and antifungal activity.
Table 1
Sample Tested
Microorganisms
FUNGI
Standard (30 µg / ml)
9b
12
13a
13c
Itraconazole Clotrimazole
Aspergillus fumigatus
(RCMB 002003)
Geotrichum candidum
(RCMB 052006)
15.3±
0.09
13.4±
0.05
19.3±
0.09
17.4±
0.10
16.5±
0.08
14.8±
0.05
22.0±
0.10
20.2±
0.50
28±0.05
27 ±0.1
26 ± 0.1
23 ± 0.3

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HETEROCYCLES, Vol. 83, No. 3, 2011
Candida albicans (RCMB
005002)
Syncephalastrum racem-
osum (RCMB 005003)
Gram Positive Bacteria
12.2±
0.08
NA
15.2±
0.05
NA
13.0±
0.05
NA
16.5±
0.10
NA
26 ±0.02
22 ±0.09
18 ± 0.1
20 ± 0.2
Pencillin G Streptomycin
Staphylococcus aureus
(RCMB 000106)
Bacillis subtilis (RCMB
000107)
17.9±
0.03
14.2±
0.1
20.9±
0.03
22.2±
0.04
18.9±
0.03
20.2±
0.04
23.2± 29.48 ± 0.82
0.02
24.3± 32.56 ± 0.56
0.03
25 ± 0.2
29 ± 0.4
Gram negative Bacteria
Pencillin G Streptomycin
Pseudomonas aeruginosa
(RCMB 000102)
Escherichia coli
NA
NA
NA
NA
28.32 ± 0.10
24 ± 0.1
25 ± 0.3
11.4±
0.04
17.8±
0.1
12.4±
0.09
19.4± 33.56 ± 0.78
0.50
(RCMB 000103)
NA: No activity, data are expressed in the form of mean ± SD.
Mean zone of inhibition in mm ± Standard deviation beyond well diameter (6 mm) produced on a range
of environmental and clinically pathogenic microorganisms using (10 mg/mL) concentration of tested
samples.
The results depicted in Table 1 revealed that most of the tested compounds displayed variable inhibitory
effects on the growth of the tested Gram-positive bacteria and Gram-negative bacteria strains and also
against fungal strains. In general, most of the tested compounds revealed better activity against the Gram-
positive bacteria rather than the Gram-negative bacteria and all compounds exhibited almost and no
activity against Syncephalastrum racemosum and Pseudomonas aeruginosa.
Compounds 12 and 13c showed promising results. Substitution at C-4 with phenyl or styryl substituent
with electron withdrawing group in para position increased the activity. Also, substitution at C-6 with
1-cyano-2-(phenylamino)-2-thioxoethyl or styryl group increased the activity.
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