Synthesis and antimicrobial evaluation of new thiophene and 1,3,4-thiadiazole derivatives

Article abstract of DOI:10.3987/COM-08-11512

A Facile route to some new thiophene derivatives via the reaction of 3-mercapto-2-(1-methylbenzimidazole-2-carbonyl)-3-phenylaminopropenal (3) with 1-aryl-2-bromoethanones, chloroacetonitrile and ethyl bromoacetate is reported. Reaction of 3 with hydrazon

Full text of DOI:10.3987/COM-08-11512

HETEROCYCLES, Vol. 78, No. 1, 2009
151
HETEROCYCLES, Vol. 78, No. 1, 2009, pp. 151 - 159. © The Japan Institute of Heterocyclic Chemistry
Received, 2nd August, 2008, Accepted, 12th September, 2008, Published online, 18th September, 2008.
DOI: 10.3987/COM-08-11512
SYNTHESIS AND ANTIMICROBIAL EVALUATION OF NEW
THIOPHENE AND 1,3,4-THIADIAZOLE DERIVATIVES
Mohamed R. Shaaban, Tamer S. Saleh, and Ahmad M. Farag*
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613,
Egypt
*Corresponding author: E-mail: afarag49@yahoo.com
Abstract – A Facile route to some new thiophene derivatives via the reaction of
3-mercapto-2-(1-methylbenzimidazole-2-carbonyl)-3-phenylaminopropenal (3)
with 1-aryl-2-bromoethanones, chloroacetonitrile and ethyl bromoacetate is
reported. Reaction of 3 with hydrazonoyl halides afforded 1,3,4-thiadiazole
derivatives incorporating a benzimidazole moiety. Antimicrobial and antifungal
activities of selected examples of the new products were evaluated.
INTRODUCTION
Enaminones are readily obtainable building blocks and their utility in heterocyclic synthesis has received
a considerable interest.1-7 Although the utility of the electron deficient C-1 and C-3 in enaminones
towards nucleophiles has been extensively investigated, a little has been reported on reactivity of the
electron rich C-2 in these compounds.8,9 On the other hand, benzimidazole derivatives are among
heterocyclic ring systems that have a wide range of unique pharmacological and biological potentialities.
Some of benzimidazole derivatives are now included in many of commercialized drugs.10-11
In continuation of our recent interest in the synthesis of heterocycles containing benzimidazole moiety,6,12
we report here on the reaction of the versatile E-1-(1-methylbenzimidazol-2-yl)-3-N,N-
dimethylaminoprop-2-enone (1) with phenyl isothiocyanate and the uitillity of the product 3-mercapto-2-
(1-methylbenzimidazole-2-carbonyl)-3-phenylaminopropenal (3) in the synthesis of the titled compounds.
RESULTS AND DISCUSSION
When E-1-(1-methylbenzimidazol-2-yl)-3-N,N-dimethylaminoprop-2-enone (1) was treated with phenyl
isothiocyanate, in the presence of potassium hydroxide, it afforded the corresponding potassium salt 2.
The latter product was converted into 3-mercapto-2-(1-methylbenzimidazole-2-carbonyl)-3-
phenylaminopropenal (3) upon treatment with hydrochloric acid (Scheme 1).

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HETEROCYCLES, Vol. 78, No. 1, 2009
Me
N
Me
C
Me
N
O
S
S
OH
O
N
N
O
N
N
N
PhHN
NMe2
KOH
NMe2
NMe2
1
Me
N
Me
Me
O
N
O
N
O
S
HCl
KOH
OH
NMe2
N
N
CHO
S K
CHO
N
PhHN
PhHN
-NHMe2
PhHN
SH
3
2
Scheme 1
The IR spectrum of compound 3 showed bands at 3346, 1670 and 1655 cm-1 due to NH group and two
carbonyl functions, respectively. A plausible mechanism for the formation of compound 3 is outlined in
Scheme 1.
Compound 3 reacts with 1-aryl-2-bromoethanones 4a,b in the presence of an equivalent amount of
triethylamine to afford the corresponding thiophene derivatives 5a,b (Scheme 2).
Me
Me
ArCOCH2Br
N
O
O
N
4a,b
N
N
CHO
Ar
PhHN
PhHN
S
SH
O
3
5a,b
4, 5
a, Ar = Ph
b, Ar = 4-NO2C6H4
Scheme 2
The structures of the products 5a,b were established by their elemental analysis and spectral data. For
example, the IR spectrum of the compound 5a showed an absorption band at 3323 cm-1 due to NH group
and two strong absorption bands at 1675, 1645 cm-1 due to two carbonyl functions. The mass spectra of
the isolated products showed, in each case, a peak corresponding to the molecular ion (see Experimental
Part).
Similarly, compound 3 reacts with ethyl 2-bromoacetate (6) to afford 3-(1-methylbenzimidazol-2-
yl)carbonyl-2-phenylaminothiophene-5-ethyl carboxylate (7) (Scheme 3). The structure of the latter
product was assigned on the basis of its 1H NMR spectrum which revealed a triplet signal at δ 1.13 and a
quartet signal at δ 4.12 (J = 6.9 Hz) characteristic for CH3CH2-protons. Its IR spectrum showed band at
3319 cm-1 due to NH group. The mass spectrum of the same product revealed a peak corresponding to its

HETEROCYCLES, Vol. 78, No. 1, 2009
153
molecular ion at m/z 405. In a similar manner, compound 3 reacts with chloroacetonitrile (8) to give the
corresponding 5-cyano-3-(1-methylbenzimidazol-2-yl)carbonyl-2-phenylaminothiophene (9) (Scheme 3).
The IR spectrum of the latter product revealed an absorption band at 3332 cm-1 due to NH group and a
strong absorption band at 2192 cm-1 due to nitrile function.
3
ClCH2CN
BrCH2CO2Et
8
6
Me
Me
O
O
N
N
N
N
OEt
PhHN
PhHN
CN
S
S
O
9
7
Scheme 3
Treatment of the potassium salt intermediate 3 with N-phenylbenzohydrazonoyl chloride (10) afforded a
single product (as examined by TLC) which was identified as 3,5-diphenyl-2-(1-methylbenzimidazol-2-
oyl-2-formylmethylidene)-2,3-dihydro-1,3,4-thiadiazole (11) (Scheme 4).
Me
Me
O
N
Cl
Ph
O
H
N
N
N
N
+
CHO
S K
Ph
N
Ph
N
N
PhHN
OHC
S
Ph
10
Me
2
11
HCl
10
O
N
Et3N/EtOH
N
CHO
PhHN
SH
3
Scheme 4
The structure of compound 11 was supported by its alternate synthesis from the reaction of 3-mercapto-2-
(1-methylbenzimidazole-2-carbonyl)-3-phenylaminopropenal (3) with the hydrazonoyl chloride 10 in the
presence of triethylamine (Scheme 4).
In a similar manner, the hydrazonoyl halides 12a-e react with the potassium salt intermediate 3, to afford,
the corresponding thiadiazole derivatives 15a,b (Scheme 5). The structure of thiadiazole derivatives 15a-
1
e was assigned on the basis of their elemental analysis and spectral data. For example, the H NMR

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HETEROCYCLES, Vol. 78, No. 1, 2009
spectrum of compound 15a, revealed a triplet signal at δ 1.25 and a quartet signal at δ 4.06 (J = 6.9 Hz)
characteristic for CH3CH2-protons. The mass spectrum of the same compound revealed a peak
corresponding to its molecular ion at m/z 434. Also, its IR spectrum showed three strong absorption bands
at 1680, 1665, 1650 cm-1 and 2759 cm-1, due to three carbonyl functions and CH of formyl group,
respectively.
Me
Me
N
O
N
Ar
O Ph
Cl
H
N
NH
S
HN
R
N
+
N
Ar
N
N
CHO
OHC
O
PhHN
O
+
S K
R
13
12
2
Me
N
Me
H
Ar
O
N
Ar
O
N
-PhNH2
N
N
S
PhHN
O
N
N
N
R
OHC
S
R
H
O
O
15a-e
14
Ar
15
R
a
b
c
d
e
Ph
Ph
Ph
4-MeC6H4
4-ClC6H4
OEt
PhNH
Me
Me
Me
Scheme 5
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 deuterated chloroform
(CDCl3) or 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 enaminone 1,6 1-aryl-2-bromoethanones 4a,b,13 and hydrazonyl halids 10, 12a-e14-17 were prepared
according to the reported literature.
3-Mercapto-2-(1-methyl benzimidazol-2-oyl)-3-phenylaminopropenal (3)
To a stirred solution of KOH (0.56 g, 10 mmol) in DMF (20 mL), E-1-(1-methylbenzimidazol-2-yl)-3-

HETEROCYCLES, Vol. 78, No. 1, 2009
155
N,N-dimethylaminoprop-2-enone 1 (2.29 g, l0 mmol) was added. After stirring for 30 min., phenyl
isothiocyanate (1.35 g, 10 mmol) was added to the resulting mixture. Stirring was continued for 6 h, and
then poured over crushed ice containing HCl. The solid product so formed was filtered off, washed with
water, dried and finally crystallized from EtOH/DMF to afford 3-mercapto-2-(1-methylbenzimidazol-2-
oyl)-3-phenylaminopropenal (3); Yield: 60%, mp 115-116 ˚C; IR (KBr) υmax /cm-1: 3346 (NH), 2760 (CH
formyl) 2590 (SH), 1670, 1655 (2CO); 1H NMR, (CDCl3) δ 3.21 (s, 3H, CH3), 6.93-7.56 (m, 9H, Ar H’s),
9.56 (s, 1H, CHO), 9.89 (1s, 1H, SH, D2O-exchangable), 11.25 (1s, 1H, NH, D2O-exchangable). MS
(m/z) 337 (M+, 44%). Anal. Calcd for C18H15N3O2S: C, 64.08; H, 4.48; N, 12.45; S, 9.50. Found: C,
64.23; H, 4.39; N, 12.43; S, 9.46.
Reaction of 3-mercapto-2-(1-methylbenzimidazol-2-oyl)-3-phenylaminopropenal (3), with 1-aryl-2-
bromoethanone 4a,b ethyl bromoacetate 6 and with chloroacetonitril 8
General Procedure. To a solution of compound 3 (0.33 g, 1 mmol) and an appropriate 1-aryl-2-
bromoethanone 4, ethyl bromoacetate (6) or chlorocetonitrile (8) (1 mmol), in EtOH (20 mL), and
triethylamine (0.5 mL) was added. The reaction mixture was refluxed for 4-6 h, and then allowed to cool.
The formed solid product was filtered off, washed with EtOH and recrystallized from DMF/H2O to afford
the corresponding thiophene derivatives 5a,b, 7 and 9, respectively.
5-Benzoyl-3-(1-methylbenzimidazol-2-oyl)-2-phenylaminothiophene (5a)
Yield: 84%; mp 197-198 ˚C; IR (KBr) υmax /cm–1: 3323 (NH), 1675, 1645 (2 CO); 1H NMR, (DMSO-d6)
δ 3.96 (s, 3H, N-CH3), 6.35 (s, 1H, Thiophene-4-CH), 7.11-7.72 (m, 14H, ArH’s), 10.86 (s, 1H, NH,
D2O- exchangeable). 13C NMR, δ 31.95, 110.25, 111.80, 114.89, 116.58, 121.28, 123.08, 126.85, 134.58,
134.95, 138.26, 140.25, 141.58, 142.00, 144.87, 159.46, 166.25, 179.85, 186.03. MS (m/z) 437 (M+,
41%). Anal. Calcd for C26H19N3O2S: C, 71.38; H, 4.38; N, 9.60; S, 7.33. Found: C, 71.49; H, 4.33; N,
9.58; S, 7.29.
3-(1-Methylbenzimidazol-2-oyl)-5-(4-nitrobenzoyl)-2-phenylaminothiophene (5b)
Yield: 82%; mp 220-222 ˚C; IR (KBr) υmax /cm–1: 3390 (NH), 1670, 1650 (2 CO); 1H NMR, (DMSO-d6)
δ 3.90 (s, 3H, N-CH3), 6.52 (s, 1H, Thiophene-4-CH), 7.01-7.56 (m, 13H, ArH’s), 10.99 (s, 1H, NH,
D2O-exchangeable). 13C NMR, δ 31.92, 110.85, 112.58, 114.80, 117.09, 121.28, 122.98, 127.55, 134.56,
137.76, 140.88, 142.00, 142.58, 144.87, 150.20, 157.92, 166.25, 179.55, 185.01. MS (m/z) 482 (M+,
54%). Anal. Calcd for C26H18N4O4S: C, 64.72; H, 3.76; N, 11.61; S, 6.65. Found: C, 64.85; H, 3.73; N,
11.56; S, 6.60.
3-(1-Methylbenzimidazol-2-oyl)-2-phenylaminothiophene-5-ethylcarboxylate (7)
Yield: 85%; mp 214-215 ˚C; IR (KBr) υmax /cm–1: 3319 (NH), 1720, 1650 (2 CO); 1H NMR, (DMSO-d6)
δ 1.13 (t, 3H, CH3, J = 6.9 Hz), 3.96 (s, 3H, N-CH3), 4.12(q, 2H, CH2, J = 6.9 Hz), 6.46 (s, 1H,
thiophene-4-CH), 7.27-7.75 (m, 9H, ArH’s), 10.25 (s, 1H, NH, D2O-exchangable). 13C NMR, δ 18.25,
31.92, 58.72, 110.22, 111.95, 114.21, 114.39, 121.28, 127.55, 129.55, 132.98, 134.56, 136.89, 140.05,

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HETEROCYCLES, Vol. 78, No. 1, 2009
143.90, 159.92, 175.15, 181.21. MS (m/z) 405 (M+, 29%). Anal. Calcd for C22H19N3O3S: C, 65.17; H,
4.72; N, 10.36; S, 7.91. Found: C, 65.22; H, 4.81; N, 10.25; S, 7.88.
5-Cyano-3-(1-methylbenzimidazol-2-oyl)-2-phenylaminothiophene (9)
Yield: 80%; mp 179-180 ˚C; IR (KBr) υmax /cm–1: 3332 (NH), 2192 (CN), 1670 (CO); 1H NMR, (DMSO-
d6) δ 3.62 (s, 3H, N-CH3), 6.59 (s, 1H, thiophene-4-CH), 7.11-7.65 (m, 9H, ArH’s), 9.28 (s, 1H, NH,
D2O-exchangable). 13C NMR, δ 31.92, 110.22, 111.95, 112.85, 114.21, 114.39, 121.28, 123.55, 132.98,
134.56, 136.89, 142.58, 144.90, 159.92, 178.15. MS (m/z) 358 (M+, 38%). Anal. Calcd for C20H14N4OS:
C, 67.02; H, 3.94; N, 15.63; S, 8.95. Found: C, 67.13; H, 3.86; N, 15.57; S, 8.98.
Reaction of 3-mercapto-2-(1-methylbenzimidazol-2-oyl)-3-phenylaminopropenal (3) or its
potassium salt intermediate 2, with hydrazonyl halid 10 or 12a-e
General procedure: Method A. To a solution of compound 3 (0.33 g, 1 mmol) in EtOH (20 mL), and an
appropriate hydrazonoyl halide 10 or 12 (1 mmol), triethylamine (0.5 mL) was added. The reaction
mixture was heated under reflux, where a colored precipitate started to take place within 5-20 min.,
heating was continued for further 2 h, then the reaction mixture allowed to cool. The formed solid was
filtered off, washed with EtOH and recrystallized from EtOH/DMF to afford the corresponding
thiadiazole derivatives 11 and 15a-e respectively in 80-85% yields.
Method B. The appropriate hydrazonoyl halide 10 or 12 (10 mmol) was added portionwise over a period
of 30 min. to a solution of potassium salt intermediate 2, and the reaction mixture was stirred for 12 h,
during which hydrazonyl halide dissolved and a yellowish-red colored product preciptated. The solid
product was filtered off, washed with water, dried and recrystallized from EtOH/DMF to afford products
identical in all respect (mp, mixed mp and spectra) with those obtained by method A above.
3,5-Diphenyl-2-(1-methylbenzimidazol-2-oyl-2-formylmethylidene)-2,3-dihydro-1,3,4-thiadiazole
(11)
Yield: 81%; mp 231-233 ˚C; IR (KBr) υmax /cm–1: 2753 (CH formyl), 1665, 1652 (2 CO), 1590 (C=N); 1H
13
NMR, (DMSO-d6) δ 3.81 (s, 3H, N-CH3), 7.17-7.88 (m, 14H, ArH’s), 9.79 (s, 1H, CHO). C NMR, δ
31.92, 102.56, 110.98, 114.78, 119.68, 121.87, 123.09, 127.50, 130.02, 132.55, 134.56, 136.89, 142.58,
144.90, 146.80, 166.05, 185.01, 186.00. MS (m/z) 438 (M+, 40%). Anal. Calcd for C25H18N4O2S: C,
68.48; H, 4.14; N, 12.78; S, 7.31. Found: C, 68.33; H, 4.22; N, 12.83; S, 7.33.
2-(1-Methylbenzimidazol-2-oyl-2-formylmethylidene)-3-phenyl-2,3-dihydro-1,3,4-thiadiazole-5-
ethyl carboxylate (15a)
Yield: 78%; mp 245-247 ˚C; IR (KBr) υmax /cm–1: 2759 (CH formyl), 1680, 1665, 1650 (3 CO), 1601
(C=N); 1H NMR, (DMSO-d6) δ 1.25 (t, 3H, CH3, J = 6.9 Hz), 3.66 (s, 3H, N-CH3), 4.06 (q, 2H, CH2, J =
13
6.9 Hz), 6.97-7.55 (m, 9H, ArH’s), 9.99 (s, 1H, CHO). C NMR, δ 17.09, 31.91, 59.98, 110.98, 114.78,
119.68, 121.87, 123.01, 123.09, 127.50, 132.85, 134.64, 136.89, 141.20, 146.45, 156.78, 166.89, 185.01,
186.00. MS (m/z) 434 (M+, 24%). Anal. Calcd for C22H18N4O4S: C, 60.82; H, 4.18; N, 12.90; S, 7.38.

HETEROCYCLES, Vol. 78, No. 1, 2009
157
Found: C, 60.76; H, 4.22; N, 12.83; S, 7.47.
5-(Carboxamido-N-phenyl)-2-(1-Methylbenzimidazol-2-oyl-2-formylmethylidene)-3-phenyl-2,3-
dihydro-1,3,4-thiadiazole (15b)
Yield: 80%; mp 295-297 ˚C; IR (KBr) υmax /cm–1: 3395 (NH), 2759 (CH formyl), 1680, 1669, 1650 (3
CO), 1601 (C=N); 1H NMR, (DMSO-d6) δ 3.79 (s, 3H, N-CH3), 7.07-7.88 (m, 14H, ArH’s), 9.89 (s, 1H,
CHO), 10.96 (s, 1H, NH, D2O-exchangable). 13C NMR, δ 31.91, 110.05, 114.50, 118.98, 120.85, 121.89,
122.52, 123.45, 129.50, 129.78, 132.02, 134.89, 136.05, 141.00, 146.65, 158.01, 159.99, 165.00, 186.81,
188.00. MS (m/z) 481 (M+, 34%). Anal. Calcd for C26H19N5O3S: C, 64.85; H, 3.98; N, 14.54; S, 6.66.
Found: C, 64.76; H, 3.92; N, 14.60; S, 6.75.
5-Acetyl-2-(1-methylbenzimidazol-2-oyl-2-formylmethylidene)-3-phenyl-2,3-dihydro-1,3,4-
thiadiazole (15c)
Yield: 85%; mp 278-280 ˚C; IR (KBr) υmax /cm–1: 2759 (CH formyl), 1675, 1650, 1645 (3 CO), 1598
(C=N); 1H NMR, (DMSO-d6) δ 2.55 (s, 3H, CH3), 3.67 (s, 3H, N-CH3), 7.27-7.78 (m, 9H, ArH’s), 10.02
(s, 1H, CHO). 13C NMR, δ 24.06, 31.92, 110.15, 114.00, 118.18, 120.85, 121.19, 129.78, 134.58, 136.95,
141.10, 146.55, 157.91, 159.19, 186.81, 188.00, 193.85. MS (m/z) 404 (M+, 43%). Anal. Calcd for
C21H16N4O3S: C, 62.36; H, 3.99; N, 13.85; S, 7.93. Found: C, 62.33; H, 3.92; N, 13.90; S, 7.98.
5-Acetyl-2-(1-methylbenzimidazol-2-oyl-2-formylmethylidene)-3-(4-methylphenyl)-2,3-dihydro-
1,3,4-thiadiazole (15d)
Yield: 76%; mp 258-260 ˚C; IR (KBr) υmax /cm–1: 2760 (CH formyl), 1680, 1655, 1645 (3 CO), 1606
1
(C=N); H NMR, (DMSO-d6) δ 2.25 (s, 1H, CH3), 2.79 (s, 3H, COCH3), 3.65 (s, 3H, N-CH3), 7.17-7.48
(m, 8H, ArH’s), 10.25 (s, 1H, CHO). 13C NMR, δ 20.35, 24.06, 31.92, 110.58, 114.60, 120.85,
121.65,129.05, 129.78, 134.88, 136.95, 141.10, 145.85, 157.01, 159.51, 186.90, 188.00, 193.79. MS (m/z)
418 (M+, 34%). Anal. Calcd for C22H18N4O3S: C, 63.14; H, 4.34; N, 13.39; S, 7.66. Found: C, 63.05; H,
4.29; N, 13.46; S, 7.73.
5-Acetyl-3-(4-chlorophenyl)-2-(1-methylbenzimidazol-2-oyl-2-formylmethylidene)-2,3-dihydro-
1,3,4-thiadiazole (15e)
Yield: 84%; mp 297-298 ˚C; IR (KBr) υmax /cm–1: 2760 (CH formyl), 1680, 1655, 1649 (3 CO), 1596
1
(C=N); H NMR, (DMSO-d6) δ 2.75 (s, 3H, COCH3), 3.65 (s, 3H, N-CH3), 7.03-7.58 (m, 8H, ArH’s),
13
10.35 (s, 1H, CHO). C NMR, δ 24.16, 31.92, 110.18, 114.62, 120.55, 121.55,129.15, 129.88, 134.89,
136.95, 141.10, 145.86, 157.10, 159.51, 186.91, 188.00, 193.70. MS (m/z) 438 (M+, 54%). Anal. Calcd
for C21H15ClN4O3S: C, 57.47; H, 3.44; N, 12.77; S, 7.31. Found: C, 57.56; H, 3.50; N, 12.67; S, 7.26.
BIOLOGICAL EVALUATION
The antibacterial and antifungal activity were carried out at the Microbiology Division of
Microanalytical Center of Cairo university, using the diffusion plate method.18-20 A bottomless cylinder

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containing a measured quantity (1mL, mg/mL) of the sample was placed on a plate (9 cm diameter)
containing a solid bacterial medium (nutrient agar broth) or fungal medium (Dox's medium) which has
been heavily seeded with the spore suspension of the test organism. After incubation (24 h for bacteria
and 5 days for fungi), the diameter of the clear zone of inhibition surrounding the sample is taken as
measure of the inhibitory power of the sample against the particular test organism. The test results are
depicted in Table 1.
Table 1. Antibacterial and Antifungal Activities of the Synthesized Compounds
Inhibition Zone Diameter (IZD)
(mm/mg of Compound Tested)
Gram (-)
Gram (+)
Fungus
(CA)
0.0
Compounds No.
(EC)
(SA)
Control
5a
0.0
0.0
16
++
14
++
11
++
11
++
16
++
11
++
12
++
16
++
13
++
--
16
++
13
+
14
++
12
++
11
++
11
++
13
++
12
++
11
++
12
++
12
++
18
++
--
5b
7
12
++
11
++
16
++
12
++
13
++
17
++
14
++
--
9
11
15a
15b
15c
15d
Amphotericin B
Tetracycline
26
22
+++
++
The test results are on the following basis:
The solvent used: ethanol.
Concentration of the sample in 100 µg/mL.
IZD = 2-10 mm beyond control = + (low activity).
IZD = 11-24 mm beyond control = ++ (moderate activity).
IZD = 25-35 mm beyond control = +++ (high activity).

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159
The selected compounds were tested in vitro against gram negative bacteria, Escherichia coli anaerobic
(EC), gram positive bacteria, Staphylococcus aurous (SA), and antifungal activity against Candida
albicans (CA). Tetracycline and Amphotricine were used as references antibiotics to evaluate the potency
of the tested compounds under the same condition.
The test results revealed that all compounds exhibited moderate activity against two bacterial species and
Candida albicans (CA).
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