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Vol. 59, No. 5
1489 (CꢁC, CꢁN). EI-MS m/z (%): 279 (Mꢃ, 100), 105 (20). Anal. Calcd
for C16H13N3S: C 68.79; H 4.69; N 15.04. Found: C 68.82; H 4.66; N 15.10.
2-(2-(4-Methylbenzylidene)hydrazinyl)-4-phenylthiazole (2b): Yield
83%, mp 205—206 °C. 1H-NMR (ppm) d: 2.44 (s, 3H, CH3), 6.84—7.43
(m, 10H, Ar-Hꢃthiazole-H), 7.87 (s, H, CHꢁN), 11.47 (s, 1H, NH). IR
(cmꢀ1): 3172 (NH), 1622, 1562, 1512 (CꢁC, CꢁN). EI-MS m/z (%): 294
(Mꢃ, 100), 159 (25), 120 (19), 104 (20). Anal. Calcd for C17H15N3S: C
69.59; H 5.15; N 14.32. Found: C 69.67; H 5.11; N 14.41.
2-(2-(4-Bromobenzylidene)hydrazinyl)-4-phenylthiazole (2c): Yield 87%,
mp 237—238 °C. 1H-NMR (ppm) d: 6.86 (d, 2H, Jꢁ8.1 Hz, Ar-H), 7.83 (d,
2H, Jꢁ8.1 Hz, Ar-H), 7.01—7.43 (m, 6H, Ar-Hꢃthiazole-H), 7.92 (s, H,
CHꢁN), 11.50 (s, 1H, NH). IR (cmꢀ1): 3299 (NH), 1599, 1570, 1481
(CꢁC, CꢁN), EI-MS m/z (%): 360 (Mꢃ3, 35), 359 (M+2, 100), 358
(Mꢃ1, 32), 357 (Mꢃ, 95). Anal. Calcd for C16H12BrN3S: C 53.64; H 3.38; N
11.73. Found: C 53.69; H 3.41; N 11.69.
2-(2-(4-Hydroxybenzylidene)hydrazinyl)-4-phenylthiazole (2d): Yield
83%, mp 241—243 °C. 1H-NMR (ppm) d: 6.94—7.70 (m, 10H, Ar-Hꢃthia-
zole-H), 7.97 (s, H, CHꢁN), 8.96 (s, 1H, –OH), 11.51 (s, 1H, NH). IR
(cmꢀ1): 3092 (NH), 1602, 1574, 1493 (CꢁC, CꢁN). EI-MS m/z (%): 295
(Mꢃ, 100), 175 (20), 120 (20). Anal. Calcd for C16H13N3OS: C 65.06; H
4.44; N 14.23. Found: C 65.11; H 4.41; N 14.19.
2-(2-(2-Hydroxybenzylidene)hydrazinyl)-4-phenylthiazole (2e): Yield
85%, mp 211—213 °C. 1H-NMR (ppm) d: 6.90—7.84 (m, 10H, Ar-Hꢃthia-
zole-H), 8.61 (s, H, CHꢁN), 9.91 (s, H, OH), 11.46 (s, 1H, NH). IR (cmꢀ1):
3275 (NH), 2866, 1623, 1558, 1494 (CꢁC, CꢁN). EI-MS m/z (%): 295
(Mꢃ, 100), 176 (30), 107 (20). Anal. Calcd for C16H13N3OS: C 65.06; H
4.44; N 14.23. Found: C 65.03; H 4.47; N 14.27.
the diameter of the observed inhibition zones.
Antifungal Screening Using a standard disc diffusion method, 2-aryli-
denehydrazinyl-4-arylthiazole analogues were tested in vitro for their anti-
fungal properties toward Candida albicans, Aspergillus oryzae, and Saccha-
romyces cerevis.27) Briefly, potato dextrose agar (Scharlau Chemi SA,
U.S.A.) was used as basal medium for testing of fungi. Sterilized melted
PDA medium (ca. 45 °C) was poured into a petridish (90 mm) and solidified.
Prepared discs of samples were placed gently on solidified agar plates, and
freshly seeded with the test organisms using sterile forceps. Discs with
DMSO and kanamycin were used as negative and positive controls, respec-
tively. Plates were incubated at 30ꢄ1 °C for 72 h. DMSO was used as a sol-
vent for preparation of desired solutions of the test samples.
Computational Methods The molecular geometries of the thiazole
analogues were built with a standard bond length and angles using Chem-
Bio3D ultra Ver. 12 molecular modeling program (CambridgeSoft Corpora-
tion, Cambridge, MA 02140, U.S.A.). The energy was minimized by semi-
empirical molecular orbital PM3 method28) and then by the Hartree–Fock
method at 6-31G basis set with R-Closed-Shell wave function using
GAMESS Interface in the ChemBio3D ultra Ver. 12. Muliken charges and
properties of frontier molecular orbitals of the compounds were analyzed
using the results calculated at RHF/6-31G level. The map of molecular
lipophilicity potential (MLP) and polar surface area (PSA) were viewed in
Molinspiration Galaxy 3D Structure Generator (ver. 2010.02 beta) using op-
timized structure generated by RHF/6-31G level.
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2-(2-(4-Nitrobenzylidene)hydrazinyl)-4-phenylthiazole (2f): Yield 70%,
1
mp 250—251 °C. H-NMR (ppm) d: 6.45—7.62 (m, 10H, Ar-Hꢃthiazole-
H), 7.66 (s, H, CHꢁN), 11.81 (s, 1H, NH). IR (cmꢀ1): 3145 (NH), 1622,
1557, 1506 (CꢁC, CꢁN). EI-MS m/z (%): 325 (Mꢃ, 100), 107 (20). Anal.
Calcd for C16H12N4O2S: C 59.25; H 3.73; N17.27. Found: C 59.27; H 3.79;
N 17.30.
2-(2-(3-Nitrobenzylidene)hydrazinyl)-4-phenylthiazole (2g): Yield 75%,
1
mp 228—230 °C. H-NMR (ppm) d: 6.92—8.14 (m, 10H, Ar-Hꢃthiazole-
H), 8.42 (s, H, CHꢁN), 11.61 (s, 1H, NH). IR (cmꢀ1): 3166 (NH), 2922,
1602, 1525, 1483 (CꢁC, CꢁN). EI-MS m/z (%): 325 (Mꢃ, 100), 107 (20).
Anal. Calcd for C16H12N4O2S: C 59.25; H 3.73; N 17.27. Found: C 59.23; H
3.80; N 17.32.
2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-phenylthiazole (2h): Yield 87%,
mp 199—200 °C. 1H-NMR (ppm) d: 6.86 (d, 2H, Jꢁ7.9 Hz, Ar-H), 7.83 (d,
2H, Jꢁ7.9 Hz, Ar-H), 7.08—7.43 (m, 6H, Ar-Hꢃthiazole-H), 11.50 (s, 1H,
NH). IR (cmꢀ1): 3299 (NH), 1599, 1570, 1481 (CꢁC, CꢁN). EI-MS m/z
(%): 315 (Mꢃ2, 40), 313 (Mꢃ, 100). Anal. Calcd for C16H12ClN3S: C 61.24;
H 3.85; N 13.39. Found: C 61.28; H 3.82; N 13.34.
2-(2-(2-Chlorobenzylidene)hydrazinyl)-4-phenylthiazole (2i): Yield 85%,
1
mp 234—235 °C. H-NMR (ppm) d: 6.90—7.84 (m, 10H, Ar-Hꢃthiazole-
H), 8.62 (s, 1H, CHꢁN), 11.46 (s, 1H, NH). IR (cmꢀ1): 3305 (NH), 1589,
1564, 1483 (CꢁC, CꢁN). EI-MS m/z (%): 315 (Mꢃ2, 39), 313 (Mꢃ, 100).
Anal. Calcd for C16H12ClN3S: C 61.24; H 3.85; N 13.39. Found: C 61.27; H
3.84; N 13.33.
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2-(2-(4-Methoxybenzylidene)hydrazinyl)-4-phenylthiazole (2j): Yield
83%, mp 204—205 °C. H-NMR (ppm) d: 2.94 (s, 3H, OCH3), 6.84—7.43
(m, 10 H, Ar-Hꢃthiazole-H), 8.01 (s, 1H, CHꢁN), 11.48 (s, 1H, NH). IR
(cmꢀ1): 3202 (NH), 1622, 1562, 1512 (CꢁC, CꢁN). EI-MS m/z (%): 309
(Mꢃ, 100), 175 (15), 120 (29), 107 (20). Anal. Calcd for C17H15ON3S: C
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1
2-(2-(4-N,N-Dimethylbenzylidene)hydrazinyl)-4-phenylthiazole (2k):
Yield 84%, mp 207—208 °C. 1H-NMR (ppm) d: 2.98 (s, 6H, NMe2), 6.62—
7.83 (m, 10H, Ar-Hꢃthiazole-H), 7.98 (s, 1H, CHꢁN), 11.66 (s, 1H, NH).
IR (cmꢀ1): 3109 (NH), 1615, 1543, 1508 (CꢁC, CꢁN). EI-MS m/z (%):
323 (Mꢃ, 100), 149 (20). Anal. Calcd for C18H18N4S: C 67.05; H 5.63; N
17.38. Found: C 67.03; H 5.59; N 17.32.
Antibacterial Screening In vitro bactericidal activity of novel 2-aryli-
denehydrazinyl-4-arylthiazole analogues was determined by the Kirby–
Bauer disc diffusion method.27) Briefly, nutrient agar (NA) media (Difco)
was used as basal medium for test bacteria. These agar media were inocu-
lated with 0.2 ml of the 24 h liquid cultures containing microorganisms.
Sample discs were placed gently on pre-inoculated agar plates and
Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, and E.
coli were incubated aerobically at 37 °C and Bacillus cereus, Shigella dysen-
teriae, Bacillus subtilis, and Bacillus megaterium at 30 °C for 24 h. Discs
with only dimethyl sulfoxide (DMSO) were used as a control and kanamycin
was used as a positive control. Inhibitory activity was measured (in mm) as
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Leone S., Mutti C., Kazantsev A., Sturlese M., Moro S., Cattaneo E.,
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