1510
B.F. Abdel-Wahab et al. / European Journal of Medicinal Chemistry 46 (2011) 1505e1511
3.1.11.2. Method B. A mixture of 2 (0.27 g, 1 mmol), chloroacetic
acid (0.1 g, 1 mmol) and appropriate aldehydes (1 mmol) in glacial
acetic acid (20 mL) containing anhydrous sodium acetate (0.33 g,
4 mmol) was heated under reflux for 5 h. The reaction mixture was
left to cool and the formed solid was filtered off, washed with
water, dried and recrystallized from suitable solvent.
exchangeable) 14.34 (s, H, NH, D2O-exchangeable); MS m/z (%): 517
(Mþ, 39), 104 (100).
3.1.19. 3-[3-(Benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl]-2-
cyano-N0-[1-(5-methyl-2-phenyl-1H-imidazol-4-yl)ethylidene]
acrylohydrazide (14b)
IR (KBr) nmax/cmꢁ1 3319e3128 (2NH); 2220 (CN), 1689 (C]O),
3.1.12. 5-(4-Fluorobenzylidene)-2-{[1-(5-methyl-2-phenyl-1H-
imidazol-4-yl)ethylidene]hydrazono}thiazolidin-4-one (10a)
IR (KBr) nmax/cmꢁ1 3321e3049 (2NH), 1703(C]O); 1H NMR
1H NMR (DMSO-d6)
d 2.18 (s, 3H, CH3), 2.87 (s, 3H, CH3), 6.8 (s, 1H,
benzofuryl-CH), 7.31e8.36 (m,14H, Ar-H), 8.96 (s, 1H, CH]N), 12.35
(s, H, NH, D2O-exchangeable) 13.96 (s, H, NH, D2O-exchangeable);
MS m/z (%): 551 (Mþ, 23), 104 (100).
(DMSO-d6)
d 2.51 (s, 3H, CH3), 2.93 (s, 3H, CH3), 3.92 (s, 1H, NH,
D2O-exchangeable), 7.20e7.85 (m, 9H, Ar-H), 8.42 (s, 1H,
CH ¼ Ne),11.99 (s, H, NH, D2O-exchangeable); MS m/z (%): 419 (Mþ,
39), 56 (100).
3.1.20. 7-Hydroxy-2-imino-N0-[1-(5-methyl-2-phenyl-1H-
imidazol-4-yl)ethylidene]-2H-chromene-3-carbohydrazide (15)
IR (KBr) nmax/cmꢁ1 3319e3128 (NH); 1661 (C]O), 1H NMR
3.1.13. 2-{[1-(5-Methyl-2-phenyl-1H-imidazol-4-yl)ethylidene]
hydrazono}-5-((1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)
methylene)thiazolidin-4-one (10b)
(DMSO-d6) d 2.21 (s, 3H, CH3), 2.80 (s, 3H, CH3), 6.68e7.90 (m, 8H,
Ar-H), 8.41 (s, 1H, CH), 8.97 (s, H, NH, D2O-exchangeable), 10.8 (s,
1H, OH, D2O-exchangeable) 12.53 (s, H, NH, D2O-exchangeable)
IR (KBr) nmax/cmꢁ1 3356e3044 (2NH), 1699 (C]O); 1H NMR
13.23 (s, H, NH, D2O-exchangeable); 13C NMR (DMSO-d6)
d 12.44,
(DMSO-d6)
d
2.48 (s, 3H, CH3), 2.90 (s, 3H, CH3), 3.95 (s, 1H, NH,
15.04, 39.87, 40.03, 40.20, 101.80, 111.33, 113.25, 116.30, 125.08,
128.43, 129.25, 130.85, 132.03,135.58, 142.42, 143.52, 151.98,155.85,
156.92, 158.37, 163.10.
D2O-exchangeable), 7.21e7.84 (m, 8H, Ar-H), 8.62 (s, 1H, CH]
Ne),12.39 (s, H, NH, D2O-exchangeable); 13C NMR (DMSO-d6)
d
13.00, 16.03, 39.72, 39.88, 40.05, 40.21, 40.35, 96.86, 100, 116.65,
119.26, 127.67, 127.73, 128.32, 129.05, 130.24, 132.04, 134.77, 139.12,
146.09; MS m/z (%): 549 (Mþ, 31), 56 (100).
3.2. Biological activities
3.1.14. 5-{[3-(Benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl]
methylene}-2-((1-(5-methyl-2-phenyl-1H-imidazol-4-yl)
ethylidene)hydrazono)thiazolidin-4-one (10c)
3.2.1. Antimicrobial activity
Chemical compounds were individually tested against a panel of
gram positive and negative bacterial pathogens. Antimicrobial tests
were carried out by the agar well diffusion method [25] using
IR (KBr) nmax/cmꢁ1 3336e3067 (2NH), 1699 (C]O); 1H NMR
(DMSO-d6)
d
2.52 (s, 3H, CH3), 2.93 (s, 3H, CH3), 4.02 (s,1H, NH, D2O-
100
m
L of suspension containing 1 ꢆ 108 CFU/mL of pathological
exchangeable), 7.45e8.23 (m,10H, Ar-H), 8.81 (s,1H, CH]Ne),11.98
tested bacteria, 1 ꢆ 106 CFU/mL of yeast and 1 ꢆ 104 spore/mL of
fungi spread on nutrient agar (NA), Sabourand dextrose agar (SDA),
and potato dextrose agar (PDA) medium respectively. After the
media had cooled and solidified, wells (10 mm in diameter) were
(s, H, NH, D2O-exchangeable); MS m/z (%): 583 (Mþ, 29), 56 (100).
3.1.15. 2-Cyano-N0-[1-(5-methyl-2-phenyl-1H-imidazol-4-yl)
ethylidene]acetohydrazide (11)
made in the solidified agar and loaded with 100
mL of tested
To a solution of 2-cyanoacetohydrazide (1.0 g, 10 mmol) in
absolute ethanol (30 mL) 4-acetyl-5-methyl-2-phenylimidazole 1
(2.00 g, 10 mmol) was added. The reaction mixture was heated
under reflux for 1 h then left to cool. The solid product formed upon
pouring onto ice/water was collected by filtration.
compound solution prepared by dissolving 100 mg of the chemical
compound in one mL of dimethyl sulfoxide (DMSO). The inculcated
plates were then incubated for 24 h at 37 ꢃC for bacteria and 48 h at
28 ꢃC for fungi. Negative controls were prepared using DMSO
employed for dissolving the tested compound. Ciprofloxacin
IR (KBr) nmax/cmꢁ1 3319 (NH); 2219 (CN), 1678 (C]O), 1H NMR
(50 mg/mL) and Ketoconazole (50 mg/mL) were used as standard for
(DMSO-d6)
d
2.32 (s, 3H, CH3), 2.89 (s, 3H, CH3), 4.08 (s, 2H, CH2),
antibacterial and antifungal activity respectively. After incubation
time, antimicrobial activity was evaluated by measuring the zone of
inhibition against the test organisms and compared with that of the
standard. The observed zone of inhibition is presented in Table 1.
Antimicrobial activities were expressed as inhibition diameter
zones in millimeters (mm) as follows: N.A. (no activity) ꢄ 4 mm;
þ(weak) ¼ 5e9 mm; þþ(moderate) ¼ 10e15 mm; þþþ(strong) ¼
16e20 mm and þþþþ(very strong) ꢅ 21 mm. The experiment was
carried out in triplicate and the average zone of inhibition was
calculated.
7.34e7.89 (m, 5H, Ar-H), 12.99 (s, H, NH, D2O-exchangeable) 13.99
(s, H, NH, D2O-exchangeable); MS m/z (%): 281 (Mþ, 29), 82 (100).
3.1.16. Synthesis of compounds 12e14
3.1.16.1. General procedures. Equimolecular mixture of 11 (2.81 g,
0.01 mol) and appropriate aldehyde (0.01 mol), in anhydrous
ethanol (20 mL) containing piperidine (0.50 mL) was heated under
reflux for 3 h. The formed solid was collected by filtration.
3.1.17. 2-Cyano-3-(4-fluorophenyl)-N0-[1-(5-methyl-2-phenyl-1H-
imidazol-4-yl)ethylidene]acrylohydrazide (12)
3.2.2. Minimal inhibitory concentration (MIC) measurement
IR (KBr) nmax/cmꢁ1 3302e3073(2NH); 2221 (CN), 1683 (C]O), 1H
The bacteriostatic activity of the active compounds (having
inhibition zones (IZ) ꢅ 16 mm) was then evaluated using the two
fold serial dilution technique [26]. Two fold serial dilutions of the
tested compounds solutions were prepared using the proper
nutrient broth. The final concentration of the solutions was 250;
NMR(DMSO-d6)d2.20(s,3H, CH3),2.78(s,3H, CH3),7.25e8.10(m, 9H,
Ar-H), 9.25 (s,1H, CH]N),12.98(s, H, NH, D2O-exchangeable)14.24 (s,
H, NH, D2O-exchangeable); MS m/z (%): 372 (Mþ, 31), 104 (100).
3.1.18. 2-Cyano-N0-[1-(5-methyl-2-phenyl-1H-imidazol-4-yl)
ethylidene]-3-[1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl]
acrylohydrazide (14a)
175; 87.5; 43.8 and 21.9 mg/mL. The tubes were then inoculated
with the test organisms, grown in their suitable broth at 37 ꢃC for
24 h for bacteria (about 1 ꢆ108 CFU/mL), each 5 mL received 0.1 mL
of the above inoculum and incubated at 37 ꢃC for 24 h. The lowest
concentration showing no growth was taken as the minimum
inhibitory concentration (MIC).
IR (KBr) nmax/cmꢁ1 3308e3103(2NH); 2221 (CN), 1681 (C]O),
1H NMR (DMSO-d6)
d
2.21 (s, 3H, CH3), 2.91 (s, 3H, CH3), 7.22e8.46
(m, 13H, Ar-H), 9.31 (s, 1H, CH]N), 12.89 (s, H, NH, D2O-