432
SALEH M. ALꢀMOUSAWI et al.
166.29, 162.08, 152.30 (2C), 134.31, 128.69 (2C),
127.69, 125.89 (2C), 107.48, 87.97. MS: (%) 257
(M+, 100), 226 (10), 200 (5), 134 (35), 128 (10), 134.31, 128.75 (2C), 127.72, 125.90 (2C), 109.66, 89.99,
90 (10). Calcd. for C12H11N5S (257.31): C, 56.01; H,
4.31; N, 27.22; S, 12.41. Found: C, 55.80; H, 4.41; N; 154 (5), 134 (30), 102 (5), 89(5), 77 (5). Calcd. for
8.01 (m, 2H, ArꢀHs), 8.07 (d, 1H,
NMR: 160.59, 156.98, 152.22, 149.36, 147.14, 146.94,
J
= 6.0, CH); 13C
m/z
88.59. MS: m/z
(%) 308 (M+, 100), 268 (30), 175 (5),
26.88; S, 11.99.
C15H12N6S (308.36): C, 58.43; H, 3.92; N, 27.25;
S, 10.40. Found: C, 58.33; H, 3.79; N; 27.20; S, 10.37.
2ꢀ(5ꢀBenzylideneꢀ4ꢀphenylthiazolꢀ2(5H)ꢀylidene)malꢀ
ononitrile (VII). An equimolar mixture of compound
) and benzylidenemalononitrile in EtOH (20 mL)
and piperidine (1 mL) was stirred under reflux for 3 h.
The reaction mixture was cooled and poured into iceꢀ
water giving a solid which was collected by filtration
and crystallized from EtOH to give the product as faint
(V
Antimicrobial Activity
Antimicrobial activity of the synthesized comꢀ
pounds was assessed using gramꢀpositive bacteria
Bacillus spp. and methicillinꢀresistant Staphylococꢀ
(
cus aureus (MRSA)), gramꢀnegative bacteria (E. coli
,
yellow crystals. Yield 77%; mp 280–282°C; IR: 22.7
(CN), 2179 (CN); 1H NMR (600 MHz): 5.84 (s, 1H,
CH), 7.15–7.42 (m, 10H, ArꢀH); 13C NMR: 169.07,
141.21, 140.04, 131.24, 130.57, 129.69, 129.21 (2C),
128.91 (2C), 128.45 (2C), 128.21, 127.94, 127.61
(2C), 124.62, 122.00, 117.17. MS: m/z (%) 313 (M+,
80), 285 (10), 235 (90), 225 (100), 178 (10), 134 (60),
98 (20). Calcd. for C19H11N3S (313.38): C, 72.82; H,
3.54; N, 13.41; S, 10.23. Found: C, 12.94; H, 3.32; N;
13.31; S, 10.19.
Pseudomonas aeruginosa, and Salmonella enterica),
and yeast (Candida albicans). Microdilution method
was used as reported by James and Jean [25]. Briefly,
the synthesized compounds at different concentraꢀ
tions in DMSO were added to shaked cultures of test
strains (10 strains of Bacillus spp.; MRSA, E. coli, and
C. albicans 20 strains each, 25 strains of S. enterica, and
50 strains of P. aeruginosa). Optical density (λ600 nm) of
the microbial cultures was measured in sterile 96 well
plates using the LD400 (Beckman Coulter, USA)
reader in the presence or absence (controls) of the
2ꢀ(4ꢀPhenylꢀ5ꢀphenylazoꢀ3Hꢀthiazolꢀ2ꢀylidene)maꢀ
lononitrile (VIII). A cold solution of benzenediazoniꢀ
um chloride (0.01 mol) was added to a solution of soꢀ
dium nitrite (0.7 g in 10 mL H2O) and a solution of
aniline hydrochloride (0.93 g, 0.01 mol of aniline and
concentrated HC1, 5 mL) with stirring at room temꢀ
perature. The resulting solution was then added to a
experimental compounds at 37°C. The minimum
inhibitory concentrations (MIC) of the compounds
were calculated. For comparative studies, effect of
antibiotics (cefotaxime, nitrofurantoin, penicillin,
and piperacillin) on the growth of test microorganisms
was examined and the results were used to determine
MIC. In addition, the doseꢀresponse curves were built
using the aforementioned method. All test microorꢀ
ganisms were isolated from medical samples collected
from hospitals in Kuwait. The strains were identified
by sequencing of the 16S [26] and 18S rRNA genes
[27]. All experiments were conducted in triplicates.
cold solution of compound (V) (2.25 g, 0.01 mol) in
ethanol (50 mL) containing sodium acetate (2 g). The
reaction mixtures was stirred for 1 h and filtered. The
solid products were crystallized from EtOH to give red
crystals. Yield 85%; mp 198–200°C; IR: 3180 (NH),
2216 (2CN); 1H NMR (400 MHz): 5.03 (br, 1H, NH,
D2O exchangeable), 7.25–7.60 (m, 8H, ArꢀH), 8.22–
8.24 (m, 2H, ArꢀH); 13C NMR: 175.46, 147.29, 138.67,
131.79, 131.47, 130.73 (2C), 130.70 (2C), 129.59
(2C), 128.63 (2C), 127.05, 118.96, 117.71, 115.70
ACKNOWLEDGMENTS
The authors are grateful Dr. Bivin Thomas for
graphical assistance and to Kuwait University
Research Administration for the financial support of
project no. SC12/13. Analytical facilities were proꢀ
vided by the GFS projects no. GS 01/01, GS 01/03,
GS 01/05, GS 02/10, and GS 03/08 and are greatly
appreciated.
(2CN). MS:
m/z
(%) 329 (M+, 100), 301 (20), 237
(15), 225 (25), 153 (5), 103 (20), 92 (25), 77 (65).
Anal. calcd. for C18H11N5S (329.38): C, 65.64; H,
3.37; N, 21.26; S, 9.73. Found: C, 65.49; H, 3.51; N,
21.15; S, 9.39.
3ꢀ(4ꢀPhenylthiazolꢀ2ꢀyl)pyrazolo[1,5ꢀa]pyrimidineꢀ
2,7ꢀdiamine (X). A mixture of (VI) (2.57 g, 0.01 mol) and
3ꢀ(piperidinꢀ1ꢀyl)acrylonitrile (IX) (1.36 g, 0.01 mol)
in DMF (10 mL) was stirred at reflux for 10 h. The reꢀ
action mixture was cooled and poured into ice water
giving a solid which was collected by filtration and
crystallized from DMF to give the product as yellow
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crystals. Yield 70%; mp 329–330
(NH2), 3355, 3263 (NH2); 1H NMR (400 MHz): 6.13
(d, 1H, = 6.0, CH), 6.62 (br, 2H, NH2, D2O exꢀ
changeable), 7.33–7.47 (m, 3H, ArꢀHs), 7.61 (br, 2H,
NH2, D2O exchangeable), 7.85 (s, 1H, thiazoleꢀH),
°C; IR: 3443, 3305
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RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 42
No. 4
2016