Synthesis, characterization, antibacterial and urease inhibition studies of some novel symmetrical N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas)

Article abstract of DOI:10.14233/ajchem.2013.14174

A series of some novel N3,N3'-bis-(disubstituted)isophthalyl-bis- (thioureas), with general formula [ C>inf<6>/infinf<4>/ inf<{CONHCSNR1R2}2], where R1 = H (4a-4d, 4f, 4g, 4i, 4j), C>inf<6>/infinf<5>/inf<(4e), C>inf<6>/ infinf<6>/ infinf<4>/infinf<6>/ infinf<4>/inf<(4c), 2-NO2 C>inf<6>/ infinf<4>/inf<(4d), C>inf<6>/ infinf<5>/inf<(4e), 2,4(CH3)2C>inf<6>/infinf<6>/infinf<6>/ infinf<4>/inf<(4j) have been synthesized in good to excellent yields by reaction of isophthaloyl isothiocyanate with primary and secondary amines using dry acetone as solvent. These compounds 3a-j have been characterized by elemental analyses, infrared and 1H NMR spectroscopy. These compounds were screened for their antibacterial activity against bacterial species, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, S. sonii, Salmonella typhi and Pseudomonas aeroginosa. Some compounds showed potent activity against some bacterial strains and others exhibited strong antibacterial activity. The synthesized compounds 4a-j were also evaluated for urease inhibition and found to exhibit varying degree of urease inhibition activity. Compounds 4a-d were found to be the most active, exhibiting IC50 = 26.3 ± 0.5 to 31.1 ± 0.3 μM. It was concluded that these compounds may be a potential source of active antibacterial agents and some of these compounds also exhibit promising urease inhibitory activity.

Full text of DOI:10.14233/ajchem.2013.14174

Asian Journal of Chemistry; Vol. 25, No. 10 (2013), 5328-5332
http://dx.doi.org/10.14233/ajchem.2013.14174
Synthesis, Characterization, Antibacterial and Urease Inhibition Studies of Some
Novel Symmetrical N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas)
1
1,*
1
2
1
MUHAMMAD JAMIL , MUHAMMAD ZUBAIR , NASIR RASOOL , ATAF ALI ALTAF , KOMAL RIZWAN ,
3
1
4,5
SAMIA HAFEEZ , IFTIKHAR HUSSAIN BUKHARI and PETER LANGER
1Department of Chemistry, Government College University, Faisalabad-38000, Pakistan
2Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan
3Department of Chemistry, Bahauddin Zakariya University, Multan-60800, Pakistan
4Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
5Leibniz Institute of Catalysis at the University of Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
*Corresponding author: Tel: +92 300 8923442; E-mail: zubairmkn@yahoo.com
(Received: 7 June 2012;
Accepted: 1 April 2013)
AJC-13198
A series of some novel N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas), with general formula [C6H4{CONHCSNR1R2}2], where R1 =
H (4a-4d, 4f, 4g, 4i, 4j), C6H5(4e), C6H11(4h) and R2 = C5H4N3(4a), 4-C6H4COOH(4b), 3-NO2C6H4(4c), 2-NO2C6H4(4d), C6H5(4e),
2,4(CH3)2C6H3(4f), C6H11(4g, 4h), C5H4N(4i), 3-NH2C6H4(4j) have been synthesized in good to excellent yields by reaction of isophthaloyl
isothiocyanate with primary and secondary amines using dry acetone as solvent. These compounds 3a-j have been characterized by
elemental analyses, infrared and 1H NMR spectroscopy. These compounds were screened for their antibacterial activity against bacterial
species, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, S. sonii, Salmonella typhi and Pseudomonas aeroginosa. Some com-
pounds showed potent activity against some bacterial strains and others exhibited strong antibacterial activity. The synthesized com-
pounds 4a-j were also evaluated for urease inhibition and found to exhibit varying degree of urease inhibition activity. Compounds 4a-d
were found to be the most active, exhibiting IC50 = 26.3 0.5 to 31.1 0.3 µM. It was concluded that these compounds may be a potential
source of active antibacterial agents and some of these compounds also exhibit promising urease inhibitory activity.
Key Words: Bisthioureas, Antibacterial activity, Synthesis, Isothiocyanate.
analgesic herbicidal15,16, plant growth regulating17, antiaggre-
INTRODUCTION
gating18, antiarrythmic, localanesthetic19, antihyperlipidemic20.
Some thioureas have been recently described as potent anti-
Urease inhibitors are considered new targets for antiulcer
drugs1. The activity of bacterial ureases has been proved to be
tumor20,21 and non-nucleoside inhibitors of HIV reverse
transcriptase22. Recently reported23 some dithiourea derivatives
important virulence factor in the development of many dange-
rous and harmful clinical conditions for human and animal
health as well as agriculture2. Bacterial ureases have been
these indicated best inhibition activities against KB and CNE2
exhibited cytotoxicity against various cancer cells and one of
reported to play a role in the formation of infectious stones3
with IC50 values of 10.72 and 9.91 micrometer respectively.
In the present paper we wish to report the synthesis, anti-
and development of peptic ulcers and stomach cancer4. Ureases
bacterial and urease inhibition activities of some new N3,N3'-
also actively contribute to the development of pyelonephritis,
urolithiasis, hepatic coma, hepatic encephalopathy andurinary
catheter encrustation5. In the near past, many compounds have
bis-[(disubstituted)isophthalyl-bis-(thioureas) compounds (4a-
j)]. The structures of the synthesized compounds were derived
been proposed as urease inhibitors to reduce environmental
by modern spectroscopic techniques and the purity of compounds
was verified by elemental analysis.
problems and enhance the uptake of urea nitrogen by plants6-9.
By urease inhibition, the treatment of infections caused by
EXPERIMENTAL
urease producing bacteria may also be possible.
Thiourea derivatives possess wide spread applications in
the field of medicine, agriculture and analytical chemistry.
These compounds exhibit a comprehensive range of biological
All chemicals used were of analytical reagent grade (AR)
and of the highest purity available. They include isophthalic
acid (Sigma), thionyl chloride (Sigma), potassium thiocya-
nate (Aldrich), adenine (Aldrich), 3-nitroaniline (Aldrich),
activities such as antiviral10,11, antibacterial12, fungicidal13,14
,

Vol. 25, No. 10 (2013)
Studies of Some Novel Symmetrical N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas) 5329
1
2-nitroaniline (Aldrich), diphenylamine (Aldrich), 2,4-
dimethylaniline (BDH), cyclohexylamine (Sigma), dicyclo-
hexylamine (Sigma), 4-aminopyridine (Aldrich), 1,3-diamino
benzene (Aldrich). The organic solvents used include acetone,
absolute ethyl alcohol and dimethyl formamide (DMF). These
solvents were either spectroscopically pure from BDH or
purified by the recommended methods and tested for their
spectral purity. De-ionized water collected from all-glass
equipment was used wherever required.
(C=C), 1540, 1332 (NO). H NMR (300 MHz, DMSO-d6,
Me4Si): δ (ppm): 11.98 (s, 2H, 2NH), 10.60 (s, 2H, 2NH),
8.30-7.40 (m, 8H, Ar-H). Anal. calcd. (%) for C22H16N6O6S2:
C, 50.38; H, 3.07; O, 16.02; S, 12.23. Found (%): C, 50.40; H,
3.11; O, 16.05; S, 12.23.
N3,N3,N3',N3'-Tetrakis(phenyl)isophthalyl-bis-(thiourea)
(4e):Yellow solid, m.p. 200 ºC; IR (KBr, νmax, cm-1); 3319 (N-
H), 1676, 1680 (C=O), 1590, 1480, 1531 (C=S), 1264, 1154
(C=S). 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm): 12.81
(s, 2H, 2NH), 8.37-7.14 (m, 24H, Ar-H). Anal. calcd. (%) for
C34H26N4O2S2: C, 69.60; H, 4.47; O, 9.55; S, 10.93; Found
(%): C, 63.68; H, 4.50; O, 9.60; S, 10.91.
Elemental microanalyses of the separated solids for C, H,
N and S were performed on a PE-2400 CHNS analyzer. The
analyses were repeated twice to check the accuracy of data.
Infrared spectra were recorded on an Alpha Centauri FT-IR
spectrophotometer in wavenumber region 4000-400 cm-1. The
N3,N3'-bis-(2,4-dimethylphenyl)isophthalyl-bis-(thio-
urea) (4f): Yellow solid, m.p. 194 ºC; IR (KBr, νmax, cm-1);
3358, 3216 (N-H), 2950 (CH3), 1660 (C=O), 1600, 1516, 1474
1
spectra were recorded as KBr pallets. The H NMR were
recorded using FT-80 instrument, DMSO-d6 was used as
solvent and Me4Si as internal standard.
1
(C=C), 1258, 1175 (C=S). H NMR (300 MHz, DMSO-d6,
Me4Si): δ (ppm): 12.22 (s, 2H, 2NH), 9.16 (s, 2H, 2NH), 8.22-
7.07 (m, 10H, Ar-H), 2.36-2.27 (m, 12H, 6CH3). Anal. calcd.
(%) for C26H26N4O2S2: C, 63.65; H, 5.34; O, 11.42; S, 13.07;
Found (%): C, 63.68; H, 5.32; O, 11.45; S, 13.10.
N3,N3'-bis-(cyclohexyl)isophthalyl-bis-(thiourea) (4g):
Yellow solid, m.p. 197 ºC; IR (KBr, νmax, cm-1); 3395 (N-H),
2970 (C-C), 1659 (C=O), 1600, 1509, 1445 (C=C), 1252, 1199
(C=S). 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm): 12.11
(s, 2H, 2NH), 9.14 (s, 2H, 2NH), 8.32-7.58 (m, 4H, Ar-H),
4.57-1.36 (m, 22H cyclohexyl). Anal. calcd. (%) for
C22H30N4O2S2: C, 59.16; H, 6.77; O, 12.54; S, 14.36; Found
(%): C, 59.20; H, 6.75; O, 12.59; S, 14.40.
N3,N3,N3',N3'-Tetrakis(cyclohexyl)isophthalyl-bis-(thio-
urea) (4h): Yellow solid, m.p. 195 ºC; IR (KBr, νmax, cm-1):
3442 (N-H), 1692 (C=O), 1602, 1585, 1469 (C=C), 1249, 1171
(C=S). 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm): 11.6
(s, 2H, 2NH), 8.49-7.62 (m, 4H, Ar-H), 3.65-1.28 (44H,
cyclohexyl). Anal. calcd. (%) for C34H50N4O2S2: C, 66.84; H,
8.25; O, 9.17; S, 10.50; Found (%): C, 66.82; H, 8.30; O, 9.20;
S, 10.55.
N3,N3'-bis-(4-pyridinyl)isophthalyl-bis-(thiourea) (4i):
Yellow solid, m.p. 192 ºC; IR (KBr, νmax, cm-1); 3299 (N-H),
1690 (C=O), 1660 (C=N), 1609, 1532, 1455 (C=C), 1270, 1150
(C=S). 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm):. 12.30
(s, 2H, 2NH), 9.90 (s, 2H, 2NH), 8.37 - 6.64 (m, 12H, Ar-H).
Anal. calcd. (%) for C20H16N6O2S2: C, 55.03; H, 3.69; O, 19.25;
S, 14.69; Found (%): C, 55.09; H, 3.71; O, 19.29; S, 14.66.
N3,N3'-bis-(3-aminophenyl)isophthalyl-bis-(thiourea)
(4j): Grey solid, m.p. 201 ºC; IR (KBr, νmax, cm-1): 3330, 3211
(N-H), 1685 (C=O), 1640, 1535, 1458 (C=C), 1270, 1148
(C=S). 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm): 12.33
(s, 2H, 2NH), 9.81 (s, 2H, 2NH), 8.25-6.47 (m, 12H, Ar-H),
5.22 (s, 4H, 2NH2). Anal. calcd. (%) for C22H20N6O2S2: C,
56.88; H, 4.34; O, 18.09; S, 13.80; Found (%); C, 56.93; H,
4.33; O, 18.16; S, 13.79.
Synthesis of N3,N3'-bis-(disubstituted) isophthalyl-bis-
(thioureas): A solution of isophthalyl chloride (2) (0.1 mol),
obtained by the reaction of isophthalic acid with thionyl
chloride, was prepared in dry acetone. Potassium thiocyanate
(0.2 mol), previously dried at 80 ºC for 2 h, was added to this
solution and stirred for 1 h at room temperature to get the
isophthaloyl isothiocyanate (3). This solution was mixed with
a solution of primary/secondary amines (0.2 mol) and stirred
for 24 h at room temperature to get the target disubstituted
bisthiourea derivatives (4a-j) in good to excellent yields
(Scheme-I). The mixture was then poured into sufficient quan-
tity of ice cold water and the product was settled as white to
yellow precipitate which were filtered, washed with cold water
and dried in vacuum desiccator. For further purification, the
products were recrystallized from DMF.
N3,N3'-bis-(7H-purin-6-yl)isophthalyl-bis-(thiourea)
(4a): White solid, m.p.: 198 ºC; IR (KBr, νmax, cm-1): 3346 (N-
H), 1740 (C=O),1690 (C=N), 1600, 1540, 1489 (C=C) 1250,
1170 (C=S), 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm):
12.12 (d, J = 3.6 Hz, 2H, NH), 11.32 (s, 2H, 2NH), 10.92 (s,
1H), 10.78 (s, 1H), 8.52 -7.56 (m, 8H, Ar-H), anal. calcd. (%)
for C20H14N12O2S2: C, 46.33; H, 2.72; N, 32.41; S, 12.37. Found
(%): C, 46.46; H, 2.72; N, 32.43; S, 12.35.
N3,N3'-bis-(4-carboxyphenyl)isophthalyl-bis-(thiourea)
(4b): White solid, m.p.: 201 ºC; IR (KBr, νmax, cm-1): 3352,
3160 (N-H, O-H), 1660 (C=O), 1600, 1530, 1459 (C=C) 1160
(C=S), 1H NMR (300 MHz, DMSO-d6, Me4Si): δ (ppm):, 12.18
(s, 2H, 2NH), 9.91 (s, 2H, 2NH), 8.32-7.47 (m, 12H, Ar-H),
15.24 (s, 6H, 2CH3), anal. calcd. (%) for C24H18N4O6S2: C,
55.16; H, 3.47; O, 10.72; S, 12.27. Found (%): C, 55.19; H,
3.45; O, 10.73; S, 12.29.
N3,N3'-bis-(3-nitrophenyl)isophthalyl-bis-(thiourea)
(4c): Yellow solid, m.p.: 203 ºC; IR (KBr, νmax, cm-1); 3375
(N-H), 1670 (C=O), 1607, 1545, 1490 (C=C), 1542, 1340
1
(NO), 1280, 1139 (C=S), H NMR (300 MHz, DMSO-d6,
Pharmacology
Me4Si): δ (ppm):. 12.36 (s, 2H, 2NH), 9.49 (s, 2H, NH), 8.47-
7.56 (m, 12H, Ar-H). Anal. calcd. (%) for C22H16N6O6S2: C,
50.38; H, 3.07; O, 16.02; S, 12.23. Found (%): C, 50.40; H,
3.10; O, 16.10; S, 12.22.
N3,N3'-bis-(2-nitrophenyl)isophthalyl-bis-(thiourea)
(4d): Yellow solid, m.p. 196 ºC; IR (KBr, νmax, cm-1): 3338
(NH), 1675, 1688 (C=O), 1260, 1152 (C=S), 1592, 1480, 1526
Test microorganisms: Bacillus subtilis, Staphylococcus
aureus, Escherichia coli, S. sonii, Salmonella typhi and Pseudo-
monas aeroginosa were used as the bacterial tested organisms.
The pure bacterial strains were obtained from the Department
ofVeterinary Microbiology, University ofAgriculture, Faisalabad,
Pakistan.

5330 Jamil et al.
Asian J. Chem.
Statistical analysis: All the experiments were conducted
in triplicate unless stated otherwise and statistical analysis of
the data was performed by analysis of variance (One Way
Anova), using STATISTICA 5.5 (Stat Soft Inc, Tulsa, Oklahoma,
USA) software. A probability value of difference p ≤ 0.05
was considered to denote a statistically significance. All data
were presented as mean values standard deviation (SD).
Urease assay and inhibition: The reaction mixtures
comprising 25 µL of Jack bean Urease solution, 55 µL of
buffers and 100 mM urea were incubated with 5 µL (1 mM
conc.) of the test compounds at 30 ºC for 15 min in well plates.
The measurement of ammonia production (indophenol
method)26 was used to determine the urease activity. The phenol
reagent (45 µ L, 1 % w/v phenol and 0.005 % w/v sodium
nitroprusside) and alkali reagent (70 µL, 0.5 % w/v sodium
hydroxide and 0.1 % NaOCl) were added to each well and the
increasing absorbance at 630 nm was measured after 50 min,
using a microplate reader (Molecular Device, USA). The
change in absorbance per min was noted and the results
processed using SoftMax Pro software (Molecular Device,
USA). All the reactions were performed in triplicate. All the
assays were performed at pH 8.2 (0.01 M K2HPO4.3H2O, 1
mM EDTA and 0.01 M LiCl2). The percentage inhibitions were
calculated from the formula 100-(ODtestwell/ODcontrol) × 100.
Thiourea was used as the standard inhibitor.
SOCl2
DMF
Heat ,
HO
OH
Cl
Cl
O
O
O
O
((CH3)2CO KSCN
O
((CH3)2CO
NHR1R2
S
N
SCN
NCS
NH
R1
NH R1
N
O
O
R2
O
S
R2
R1
R2
R1
R2
H3C
N
N
4a
4f
H
CH3
H
H
N
NH
4g
4h
4i
4b
4c
COOH
NO2
H
H
O2N
N
4d
4e
H
H
H
NH2
4j
Scheme-I: Synthesis of N3,N3’-bis-(discubstituted)isophthal-bis-(thioureas)
Antibacterial activity by disc diffusion method: Anti-
bacterial activity of compounds 4a-j was determined in vitro
by using the disc diffusion method15 against various gram-
negative and gram-positive bacteria (Table-1) at a concentration
of 200 µg/100 µL in DMSO solution. Ampicillin (100 µL/
disc) and ciprofloxacin (100µL/disc) were used as standard
drugs. 24 h old cultures, containing approximately 1.5 × 106
(CFU/mL) were spread on the surface of nutrient agar (NA)
plates. The discs (6 mm diameter) were impregnated with (100
µL/disc) test samples and then placed aseptically on the
inoculated agar media. Experimental plates were incubated at
37 ºC for 24 h.Antibacterial activity was evaluated by measuring
the diameter of the inhibition zone (IZ) and compared with
standard drugs. The inhibition zone values from 25-35 mm were
taken as potent and from 20-25 mm as strong and values greater
then 10mm were considered as moderate activity.
RESULTS AND DISCUSSION
Synthesis: The synthetic route for the newly synthesized
compounds, N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas)
(4a-j), is illustrated and outlined in Scheme-I. Isophthaloyl
chloride 2 was treated with anhydrous KSCN using dry acetone
as solvent to give isophthaloyl isothiocyanate 3 in quantitative
yield. The diisothiocynates 3 are useful synthetic building
blocks which may be efficiently used for the synthesis of N,N'-
disubstituted thioureas and benzenedicarbonyl bisthioureas24.
In the present work the isothiocynate 3 was not isolated and
treated directly with primary or secondary amines to give the
corresponding dithiourea derivatives (4a-j) in good to excellent
yields. Since the addition to -N=C=S system and nucleophilic
substitution at carbonyl-carbon atom may compete with one
another, it has been noticed that isothiocyanate 3 reacted
TABLE-1
IN VITRO ANTIBACTERIAL ACTIVITY OF THE SYNTHESIZED COMPOUNDS (4a-j) BY DISC DIFFUSION METHODa
Gram positive bacteria
Gramnegative bacteria
Compound
B. subtilis
31 0.81b
S. aureus
32 0.81b
17 1.41e
30 2.11bc
13 0.71f
-
E.coli
31 1.41b
20 0.91d
S. sonii
S. typhi
30 1.82b
13 0.41f
31 1.63b
-
P. aeroginosa
20 0.61d
4a
4b
4c
4d
4e
4f
27 0.0c
15 0.81e
21 0.63d
17 0.0e
-
-
-
29 0.81c
24 0.75c
28 0.81b
5
0.11f
-
-
-
-
-
-
32 1.63b
0.1g
22 1.63d
29 1.63c
10 0.81g
26 1.41d
-
31 1.63b
34 1.63b
11 0.22f
22 0.81d
-
29 0.0b
13 0.70f
24 0.61c
20 0.70d
-
22 0.70c
3
-
1
0.11f
4g
4h
4i
21 0.0d
23 1.08c
-
-
-
4j
-
-
-
-
-
38 0.41a
38 0.81a
36 1.82a
35 1.41a
38 1.61a
38 1.20a
36 1.63ab
37 0.0a
35 1.63a
34 0.0a
34 1.47a
33 0.0a
S1
S2
S1 = Ampicillin, S2 = Ciprofloxacin, - = NIL; aValues are mean SD of three separate experiments; Letters in superscript show the significance of
the results against single strain

Vol. 25, No. 10 (2013)
Studies of Some Novel Symmetrical N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas) 5331
additively with amines to give corresponding bisthiourea
derivatives (4a-j), while the formation of corresponding ester
was not observed in the case of 4b. The target compounds
(4a-j) were purified by recrystallization from DMF and charac-
terized by IR and 1H NMR data. The IR and 1H NMR data for
compounds (4a-j) has been reported. In IR spectrum, the C=S
peak appeared in the range of 1139 to 1199 cm-1 whereas the
N-H peaks appeared from 3208 to 3442 cm-1. Carbonyl
absorption bands were observed in the range of 1690-1657
cm-1. In 1H NMR spectra, the N1-H protons appeared as singlet
in the range δ 12.81to11.86 ppm whereas N3-H protons
appeared at δ 11.32 to 9.16 ppm, depending upon the nature
of group attached to N3. The appearance of N1-H proton at
higher frequency may be attributed to the presence of carbonyl
and thiocarbonyl groups which exert a strong deshielding
effect.
these results of urease inhibition activity, it appears that there
is no effect of basic skeleton of the molecule. However the
groups R1 and R2 attached at the terminals of basic skeleton
of molecule are seem to be responsible for variable urease
inhibition activity. The results are indicating that the presence
of some electron withdrawing group at the terminal positions
of the molecule leads to enhance urease inhibition activity of
the compound. These results of urease inhibition activity are
comparable to those reported for Chiral 3-substituted-4-amino-
5-thioxo-1H,4H-1,2, triazoles27.
TABLE-2
UREASE INHIBITORY ACTIVITY OF BIS-THIOUREAS
S. No
Compound
IC50 + SEM
28.4 0.3
26.3 0.5
26.7 0.5
31.1 0.3
50.1 0.5
83.8 0.5
720.4 0.5
168.8 0.3
NIL
1
2
4a
4b
3
4c
1
The H NMR (DMSO) spectrum revealed signals at s
4
4d
12.81-11.86 (2H, NH) in all the compounds (4a-j) which
indicates the NH group between (C=O) and (C=S) group
remains unaffected regardless group attached to terminal N
atom The aromatic protons of the parent isophthloyl group
appeared in the range δ 8.45 to 7.53 ppm.
5
4e
6
4f
7
4g
8
4h
9
4i
10
11
4j
NIL
Biology
Thiourea
21.0 0.1
Values are mean S.D of three separate experiments
Antibacterial assay: In vitro antibacterial activity of all
the synthesized compounds (4a-j) was tested against six
different bacterial strains according to the literature protocol25.
The compounds 4a, 4c and 4f exhibited potent activity against
all tested bacteria with highest inhibition zones (Table-1). 4h
showed strong activity against S. aureus, S. typhi, P. aeroginosa,
S. sonii, B. subtilis and E. coli (inhibition zone; 26, 24, 23, 22,
22, 21 mm) respectively. Moderate activity was exhibited by
4b against S. aureus, S. sonii and S. typhi, (inhibition zone;
17, 15, 13 mm) and 4d against S. sonii, S. aureus (inhibition
zone; 17, 13 mm). Other compounds were also active against
bacteria with low activity. The compounds 4e, 4i and 4j were
inactive and showed no inhibition against all bacteria. Compa-
rative results were studied by using ampicillin and ciprofloxacin
as standard antibiotics. All compounds showed less activity
as compared to standard drugs. The results of the present
investigation demonstrated significant (p < 0.05) variations in
the antibacterial activity of the compounds.
It is therefore suggested that some structural modifications
such as substitution either on central ring or on N1 nitrogen of
N3,N3'-bis-(disubstituted)isophthalyl-bis-(thioureas) or on both
simultaneously may escort to a potent lead molecule for future
research in the field of urease inhibition. Of this series the
most active compounds 4b and 4c may act as potential mole-
cules for structural modifications.
Conclusion
Some novel N3,N3'-bis-(disubstituted)isophthalyl-bis-
(thioureas) have been synthesized and characterized by analy-
1
tical and spectral (IR, H NMR) techniques. Antibacterial
activity of these compounds was studied against bacterial
strains. Some compounds showed potent activity against some
bacterial strains and others exhibited strong antibacterial
activity. It was concluded that these compounds could be a
potential source of active antibacterial agents. These compounds
were also scanned for urease inhibition activity. Some of these
these compounds exhibited promising urease inhibitory activity,
which may be due to terminal R1 and R2 groups attached to
basic skeleton of molecule.
Urease inhibition activity: The urease inhibition activity
was carried out in accordance with the literature protocol26
using thiourea as the standard inhibitor with an IC50 value of
21.0 0.1 µM. The results shown by the synthesized
compounds (4a-j) are presented in Table-2. All the scanned
compounds showed moderate to good urease inhibition activity.
Compounds 4b and 4c proved to be the most potent urease
inhibitor showing an enzyme inhibition activity with an IC50
value of 26.3 0.5 µM and 26.7 0.5 µM respectively. These
values are comparable to 21.0 0.1 µM of the standard thiourea.
The compounds 4a and 4d also exhibited comparatively good
activity showing IC50 values 28.4 0.3 µM and 31.1 0.3 µM
respectively. The leasst activity is shown by the compound 4g
showing an IC50 value of 720.4 0.5 µM, whereas compounds
4i and 4j are inactive towards urease inhibition. Compounds
4e, 4f and 4h showed moderate urease inhibition activity with
IC50 values ranging between 50.1 0.5-168.8 0.3 µM. From
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