R. Lakhan et al. / Il Farmaco 55 (2000) 331–337
333
Table 2
Characterization data of 1-aryl-3-(benzothiazol-2-yl)-2-thioureas (3)
Comp.
Ar
Yield (%)
m.p. (°C)
Molecular formula
Characteristic IR bands (cm−1
)
wNH
wCꢁS
3a
3b
3c
3d
4-BrC6H4
C6H5CH2
2-ClC6H4
4-C2H5OC6H4
95
55
51
49
221
181
155
198
C14H10BrN3S2
C15H13N3S2
C14H10ClN3S2
C16H15N3OS2
3480 m, 3340 w
3300 s, 3280 m
3240 s, 3180 m
3440 s, 3280 m
1240 m
1200 m
1210 m
1230 s
0.01 mol) and hydrazine hydrate (1.5 ml, 0.03 mol) in
30 ml of ethanol was heated in a sealed glass tube on a
water-bath for 8 h. Lead sulfide was filtered while hot
and the residue extracted with hot ethanol. The filtrates
were concentrated to get the required guanidine, which
was crystallized from ethanol to form light yellow
crystals; yield 45%, m.p. 240°C. Analysis: C16H14BrN5S
(C, H, N, S). IR (KBr, cm−1): 3420 m, 3350 w (NH2
and NH str), 1640 s, 1600 s, 1540 s, 760 m. NMR
(DMSO-d6): l 5.27 (s, 2H, NH2, D2O exchange),
6.90–8.00 (m, 10H, ar), 8.85 (s, 1H, NH, D2O
exchange), 10.79–11.66 (broad, 1H, NH, D2O ex-
change). By the above procedure, a series of 1-aryl-2-
amino-3-(4-phenylthiazol-2-yl)guanidines (2b–f) were
prepared and crystallized from ethanol. Their yields,
m.p., characteristic IR and NMR data are recorded in
Table 3.
(m, 10H, 8 ar and NH2, D2O exchange), 9.35 (s, 1H,
NH, D2O exchange), 11.35–11.88 (broad, 1H, NH,
D2O exchange).
Similarly, a series of 1-aryl-2-amino-3-(benzothiazol-
2-yl)guanidines (4b–d) were prepared. Their yields,
m.p. and characteristic IR and NMR data are recorded
in Table 4.
3. Antimicrobial screening results
The 1-aryl-2-amino-3-(4-arylthiazol-2-yl)guanidines
(2) and 1-aryl-2-amino-3-(benzothiazol-2-yl)guanidines
(4) were screened for their antimicrobial activity against
seventeen different pathogenic strains of microorgan-
isms such as Staphylococcus aureus, Staphylococcus epi-
dermidis, Escherichia coli, Klebsiella pneumoniae,
Pseudomonas aeruginosa, Citrobacter freundii, Proteus
6ulgaris, Pro6idencia rettgeri, Edwardsiela tarda,
Salmonella typhi, Salmonella typhimurium, Strigella
dysenteriae, Vibrio cholerae 01 classical, Vibrio cholerae
non 01, Vibrio parahaemolyticus, Aeromonas hydrophila
and Plesimonas shigelloides. The antimicrobial suscepti-
bility was determined by the Stokes disc diffusion tech-
nique [11] whereas minimum inhibitory concentration
(MIC) was determined by the Stokes and Ridgeway
plate dilution method [11]. Zones of inhibition of the
test microorganisms were compared with that of the
control NCTC strain of E. coli 10418.
The antimicrobial susceptibility was measured at a
concentration of 40 mg/disc. The analysis of various
patterns of susceptibility is shown in Table 5. The
results reveal that there are a wide variety of combina-
tions of the synthesized compounds to which strains
were sensitive. The synthesized N-aminoguanidines are
most active against S. epidermidis, K. pneumoniae, S.
dysenteriae, V. cholerae 01 classical, V. cholerae non 01
and A. hydrophila. In general, those aminoguanidines
which have para or meta halogen substituent in the
phenyl ring show remarkable antibacterial activity.
The sensitive aminoguanidines from antimicrobial
susceptibility test were further subjected to the MIC test
as follows. Freshly prepared solutions of synthesized
compounds diluted to different concentrations were
2.5. 1-p-Bromophenyl-2-amino-3-(4-p-tolylthiazol-
2-yl)guanidine (2g)
The guanidine was prepared from 1-p-bromophenyl-
3-(4-p-tolylthiazol-2-yl)-2-thiourea by heating for 7 h;
yield 48%, m.p. 114°C. Analysis: C17H16BrN5S (C, H,
N, S). IR (KBr, cm−1): 3450 m, 3350 m (NH2 and
NH str), 1640 m, 1600 m, 1540 s (aromatic ring),
760 s. NMR (DMSO-d6): l 2.35 (s, 3H, CH3), 6.00
(s, 2H, NH2, D2O exchange), 7.12–7.90 (m, 10H, 9 ar
and one NH, D2O exchange), 9.00 (s, 1H, NH,
D2O exchange). Similarly, a series of 1-aryl-2-amino-3-
(4-p-tolylthiazol-2-yl)guanidines (2h–k) were prepared
and crystallized from ethanol. Their yields, m.p., char-
acteristic IR and NMR (DMSO-d6) data are given in
Table 3.
2.6. 1-p-Bromophenyl-2-amino-3-(benzothiazol-
2-yl)guanidine (4a)
The compound was prepared from 1-p-bromophenyl-
3-(benzothiazol-2-yl)-2-thiourea as above. The heating
period was 6 h; yield 75%, m.p. 190°C. Analysis:
C14H12BrN5S (C, H, N, S). IR (KBr, cm−1): 3600–
3200 broad (NH2 and NH str), 1620 m, 1600 m, 1560 s
(aromatic ring), 740 m. NMR (DMSO-d6): l 6.83–8.39