Synthesis and antiurease & antioxidant activities of bis-Schiff bases of isophthalaldehyde

Article abstract of DOI:10.14233/ajchem.2016.19168

Bis-Schiff bases of iosophthalaldehyde were synthesized by reacting isophthalaldehyde with hydrazine hydrate in 1:2 ratio in ethanol for 2-3 h under reflux. Product of first step was again reacted in 1:2 ratio with different aldehyde or acetophenone yield

Full text of DOI:10.14233/ajchem.2016.19168

Asian Journal of Chemistry; Vol. 28, No. 1 (2016), 39-42
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19168
Synthesis and Antiurease & Antioxidant Activities of Bis-Schiff Bases of Isophthalaldehyde
1,*
1
2
3
4,5
FAZAL RAHIM , WASEEQ-UR-REHAMN , MUHAMMAD SHEHZAD , AJMAL KHAN , MUHAMMAD TAHA ,
1
6
7
1,*
OBAID-UR-RAHMAN ABID , MUHAMMAD TAUSEEF QUERESHI , ISFAHAN TAUSEEF and WAJID REHMAN
1Depatment of Chemistry, Hazara University, Mansehra-21120, Pakistan
2Department of Mathematics, Hazara University, Mansehra-21120, Pakistan
3Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, Pakistan
4Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300, Bandar Puncak
Alam, Selangor, Malaysia
5Faculty ofApplied Science Universiti Teknologi MARA (UiTM), 40450, ShahAlam, Selangor, Malaysia Integrative Pharmacogenomics Institute
(iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
6Department of Physics, Hazara University, Mansehra 21120, Pakistan
7Department of Microbiology, Hazara University, Mansehra 21120, Pakistan
*Corresponding authors: E-mail: sono_waj@yahoo.com; fazalstar@gmail.com
Received: 13 March 2015;
Accepted: 28 May 2015;
Published online: 5 October 2015;
AJC-17543
Bis-Schiff bases of iosophthalaldehyde were synthesized by reacting isophthalaldehyde with hydrazine hydrate in 1:2 ratio in ethanol for
2-3 h under reflux. Product of first step was again reacted in 1:2 ratio with different aldehyde or acetophenone yielding bis-Schiff bases
(1-16). All compounds were characterized by EI-MS and 1H NMR. All analogs were tested against antioxidant and urease inhibition. Few
compounds were found to showed potent antiurease and antioxidant potential.
Keywords: Schiff bases, Isophthalaldehyde, Urease inhibition, Antioxidant potential.
membrane damage occur [16]. Proteases, nucleases and protein
kinesis mechanisms are also associated with it. Oxidative
damages have also take part in human diseases. However, its
contribution to illness differs from case to case. In case of atherio-
sclerosis, it evident from literature with the chain-breaking
antioxidant probucol and from epidemiological work suggests
that oxidative damage promotes plaque development [17].
Our research group had previously reported various novel
classes’of DPPH radical scavengers [18]. In view of our previous
work we have synthesized bis-Schiff based of isophthal-
aldehyde (1-16) and evaluated for their DPPH radical and anti-
urease potential.
INTRODUCTION
Urease plays a key role in certain human and animal
diseases contributing in kidney stone, polynephritis, peptic
ulcer, gastric cancers and other ailments [1]. Urease shows its
vitality in nitrogen metabolism during plant germination [2,3].
Carbon dioxide and ammonia are formed from urea hydrolysis
in presence of urease [4-7]. Phyto-pathogenesis and loss of
ammonia results due to excessive decomposition of urea by
topsoil urease [8]. Many Schiff bases inhibit urease by decele-
rating the formation of NH4+ thus enhance the soil fertility
[9]. Due to oxidative stress, antioxidant defense system causing
the formation of reactive oxygen species [10]. Antioxidants
are helpful in healing of blood vessels membranes, normalizing
the blood flow to heart and brain as an anticancer agent, pre-
venting Alzheimer disease and dementia preventing through
radical scavenging [11-13]. Free radicals also contribute in
pathologies of artheriosclerosis, malaria and rheumatoid
arthritis and play a vital role in neurodegenerative disease and
in aging, antioxidants are used to reduce their activity [14,15].
Well known antioxidant is glutathione present in deficient
amount result in lipid peroxidation, DNA strand breaks and
EXPERIMENTAL
1H NMR spectra were recorded on AVANCE AV 300 M Hz
spectrometers. NMR spectra were recorded by using DMSO
as solvent. TMS was used as internal standard. Finingan MAT-
311A spectrometer was used for electron impact mass spectra
(EI-MS) analysis. CsI was used as an internal standard for
mass analysis. Column chromatography was performed on
silica gel (E. Merck, type 60, 70-230 mesh). Pre-coated silica
gel aluminum plates (Kieselgel 60, 2020 and 0.5 mm thick, E.

40 Rahim et al.
Asian J. Chem.
Merck, Germany) were used for TLC analysis. UV lamp of
wavelength 254 and 365 nm was used to visualize the spot in
chromatogram.
ppm): δ 10.0 (s, 2H, OH), 8.8 (d, J4,5/6,5 = 4.2 Hz, 2H, H-4/6),
8.7 (s, 1H, H-2), 8.64 (s, 2H, H-7/7′), 8.5 (s, 2H, H-8/8′), 8.0
(d, J2′,3′/6′,5′/2′,3′/6′.5′ = 7.5 Hz, 4H, H-2′/6′/2′/6′), 7.8 (m, 1H, H-
5), 6.9 (d, J3′,2′/5′,6′/3′,2′/5′,6′ = 9.9 Hz, 4H, H-3′/5′/3′/5′); EI-MS
m/z (rel. int. %): 370 (M+, 42), 147 (100), 212 (20), 120 (62),
82 (42), 65 (87).
1-((E)-((E)-(2,4-Dichlorobenzylidene)hydrazono)-
methyl)-3-((Z)-((E)-(2,4-dichloro benzylidene)hydrazono)-
methyl)benzene (7): Yield: 84 %; 1H NMR (DMSO-d6 ppm):
δ 8.9 (d, J3′,4′/3′,4′ = 10.5 Hz, 2H, H-3′/3′), 8.8 (s, 2H, H-7/7′),
8.8 (s, 2H, H-8/8′), 8.5 (s, 1H, H-2), 8.2 (d, J6′,5′/6′,5′ = 7.5 Hz,
2H, H-6′/6′), 8.05 (d, J4,5/6,5 = 5.7 Hz, 2H, H-4/6), 7.9 (m, 2H,
H-4′/4′), 7.81 (m, 2H, H-5′/5′), 7.7 (m, 1H, H-5); EI-MS m/z
(rel. int. %): 541 (M+, 42), 343 (34), 313 (100), 196 (36), 154
(65).
1-((E)-((E)-(3,4-Dimethoxybenzylidene)hydrazono)-
methyl)-3-((Z)-((E)-(3,4-dimethoxy benzylidene)hydrazono)-
methyl)benzene (8): Yield: 84 %; 1H NMR (DMSO-d6 ppm):
δ 8.8 (s, 2H, H-7/7′), 8.6 (s, 2H, H-8/8′), 8.4 (s, 1H, H-2), 8.0
(s, 2H, H-2′/2′),7.6 (m, 1H, H-5), 7.5 (d, J5′,6′/5′,6′ = 11.4 Hz,
2H, H-5′/5′), 7.3 (d, J6′,5′/6′,5′ = 7.8 Hz, 2H, H-6′/6′), 7.1 (d,
J4,5/6,5 = 8.1 Hz, 2H, H-4/6), 3.8 (s, 12H, OCH3); EI-MS m/z
(rel. int. %): 511 (M+, 42), 313 (100), 283 (69), 196 (23), 154
(44).
General procedure for synthesis of compounds 1-16:
Schiff bases were synthesized by refluxing isophthalaldehyde
with hydrazine hydrate in 1:2 in ethanol by refluxing for 2-3
h. Reaction completion was monitored by TLC. After comple-
tion of reaction the mixture was cooled, concentrated and
washed with n-hexane to obtain the pure product. This product
in second step is further reacted with different aromatic alde-
hydes/acetophenone (1:2) in refluxing ethanol for 2-3 h. Reaction
completion was monitored by TLC. These Schiff bases (1-16)
were then washed with ethyl alcohol and n-hexane to obtain
pure products
3,3′-(1E,1′E)-[(2Z,2′E)-(1,3-Phenylenebis(methan-1-yl-
1-ylidene))bis(hydrazine-2,1-diylidene)]bis(methan-1-yl-1-
ylidene)diphenol (1):Yield: 84 %; 1H NMR (DMSO-d6 ppm):
δ 9.7 (s, 2H, OH), 8.8 (s, 1H, H-2), 8.7 (s, 2H, H-2), 8.6 (s,
2H, H-7/7), 8.5 (s, 2H, H-8/8), 8.0 (m, 2H, H-5′/5), 7.7 (m,1H,
H-5), 7.5 (s, 2H, H-2/2), 7.3 (d, J4′,5′/6′,5′ = 6 Hz, 4H, H-4/6/4/
6), 6.9 (d, J4,5/6,5 = 3 Hz, 2H, H-4/6); EI-MS m/z (rel. int. %):
527 (M+, 42), 329 (100), 313 (56), 299 (73), 196 (51).
1-((E)-((E)-(4-Nitrobenzylidene)hydrazono)methyl)-3-
((Z)-((E)-(4-nitrobenzylidene)hydrazono)methyl)benzene
(2): Yield: 82 %; 1H NMR (DMSO-d6 ppm): δ 8.9 (d, J4,5/6,5
3.9 Hz, 2H, H-4/6), 8.8 (s, 1H, H-2), 8.5 (s, 2H, H-7/7′), 8.4
(d, J3′,2′/5′/6′ = 8.4 Hz, 4H, H-3′/5′/3′/5′), 8.2 (d, J2′,3′/6′,5′/2′/3′/6′,5′
=
2,2'-(1E,1’E)-1,1'-((2Z,2’E)-(1,3-Phenylenebis(methan-
1-yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(ethan-1-yl-
1
=
1-ylidene)diphenol (9): Yield: 80 %; H NMR (DMSO-d6
8.7 Hz, 4H, H-2′/6′/2′/6′), 8.1 (s, 2H, H-8/8′), 7.7 (m, 1H, H-
5); EI-MS m/z (rel. int. %): 497 (M+, 42), 299 (95), 283 (74),
196 (41), 154 (100).
ppm): δ 9.97 (s, 2H, OH), 8.8 (S, 1H, H-2), 8.0 (S, 2H, H-7/
7′), 7.8 (d, J3′,4′/6′,5′/3′,4′ = 8.4 Hz, 4H, H-3′/6′/3′/6′), 7.5 (d, J4,5/6,5
= 7.2 Hz, 2H, H-4/6),7.2 (m, 1H, H-5), 7.4 (m, 4H, H-4′/5′/4′/
5′), 2.3 (s, 6H, CH3); EI-MS m/z (rel. int. %): 526 (M+, 42),
298 (67), 283 (58), 196 (27), 154 (100).
5,5'-(1E,1’E)-((2Z,2’E)-(1,3-Phenylenebis(methan-1-
yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(methan-1-yl-
1-ylidene)bis(2-methoxyphenol) (3): Yield: 84 %; 1H NMR
(DMSO-d6 ppm): δ 9.3 (s, 2H, OH), 8.8 (s, 1H, H-2), 8.7 (s,
2H, H-7/7′), 8.6 (s, 2H, H-8/8′), 8.4 (s, 2H, H-2′/2′), 8.0 (m,
1-((E)-((E)-(1-(3-Nitrophenyl)ethylidene)hydrazono)-
methyl)-3-((Z)-((E)-(1-(3-nitro phenyl)ethylidene)hydra-
zono)methyl)benzene (10): Yield: 81 %; 1H NMR (DMSO-
d6 ppm): δ 8.8 (s, 2H, H-2′/2′), 8.7 (d, 2H, J4′,5′/4′,5′ = 6.3 Hz, H-
1H, H-5), 7.4 (d, J4,5/6,5 = 14.4 Hz, 2H, H-4/6), 7.2 (d, J6′,5′/6′,5′
=
8.1 Hz, 2H, H-6′/6′) 7.1 (d, J5′,6′/5′,6′ = 9 Hz, 2H, H-5′/5′), 3.8
(s, 6H, OCH3); EI-MS m/z (rel. int. %): 430 (M+, 42), 400
(89), 313 (100), 299 (53), 196 (48).
4′/4′), 8.4 (s, 2H, H-7/7′), 8.3 (m, 2H-5′/5′), 8.1 (d, J6′,5′/6′,5′ =
8.7 Hz, 2H, H-6′/6′),8.0 (s, 1H, H-2), 7.8 (d, J4,5/6,5 = 7.8 Hz,
2H, H-4/6), 7.68 (m, 1H, H-5),2.4 (s, 6H, CH3); EI-MS m/z
(rel. int. %): 550 (M+, 42), 317 (100), 196 (37), 154 (72), 126
(37).
4,4'-(1E,1’E)-((2Z,2’E)-(1,3-Phenylenebis(methan-1-
yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(methan-1-yl-
1
1-ylidene)dibenzene-1,2,3-triol (4): Yield: 82 %; H NMR
4,4'-(1E,1’E)-1,1'-((2Z,2’E)-(1,3-Phenylenebis(methan-
1-yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(ethan-1-yl-
(DMSO-d6 ppm): δ 11.2 (s, 2H, OH), 9.7 (s, 4H, OH), 8.8 (s,
1
2H, H-7/7′), 8.7 (s, 2H, H-8/8′), 8.5 (d, J4,5/6,5 = 10.8 Hz, 2H,
1-ylidene)dibenzene-1,3-diol (11): Yield: 84 %; H NMR
H-4/6), 8.1 (s, 1H, H-2), 7.7 (m, 1H, H-5), 6.99 (d, J6′,5′/6′,5′
=
(DMSO-d6 ppm): δ 13.5 (s, 2H, H-7/7′) 8.8 (s, 1H, H-2),8.7
(s, 2H, H-3′/3′), 8.5 (m, 1H, H-5), 7.7 (d, J4,5/6,5 = 7.5 Hz, 2H,
H-4/6), 7.6 (d, J5,6′/5′,6′ = 7.8 Hz, 4H, H-5′/6′/5′/6′), 2.41 (s, 6H,
CH3); EI-MS m/z (rel. int. %): 550 (M+, 42), 317 (100), 196
(37), 154 (72), 126 (37).
8.7 Hz, 2H, H-6′/6′), 6.5 (d, J5′,6′/5′,6′ = 6.6 Hz, 2H, H-5′/5′); EI-
MS m/z (rel. int. %): 370 (M+, 42), 299 (100), 287 (25), 154
(74), 126 (38).
1-((E)-((E)-(2,4-Dichlorobenzylidene)hydrazono)-
methyl)-3-((Z)-((E)-(2,4-dichloro benzylidene)hydrazono)-
methyl)benzene (5): Yield: 84 %; 1H NMR (DMSO-d6 ppm):
δ 8.9 (s, 2H, H-3′/3′), 8.8 (s, 2H, H-7/7′), 8.4 (s, 2H, H-8/8′),
8.2 (d, J5′,6′/5′,6′ = 8.7 Hz, 2H, H-5′/5′), 8.1 (s,1H, H-2), 7.9 (m,
4,4'-(1E,1’E)-1,1'-((2Z,2’E)-(1,3-Phenylenebis(methan-
1-yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(ethan-1-yl-
1
1-ylidene)diphenol (12): Yield: 82 %; H NMR (DMSO-d6
ppm): δ 9.7 (s, 2H, OH), 8.8 (s, 2H, H-7/7′), 8.5 (s, 1H, H-2),
8.0 (m, 1H, H-5), 7.8 (d, 4H, J3′,2′/5′,6′/3′,2′/5′,6′ = 8.4 Hz, H-3′/5′/3′/
5′) 7.7 (d, 4H, J2′,3′/6′,5′/2′,3′/6′/5′ = 8.4 Hz, H-2′/6′/2′/6′), 6.8 (d, 2H,
J4,5/6,5 = 8.4 Hz, H-4/6), 2.9 (s, 6H, H-CH3); EI-MS m/z (rel.
int. %): 511 (M+, 42), 313 (100), 283 (69), 196 (23), 154 (44).
1-((E)-((E)-(1-(4-(Piperidin-4-yl)phenyl)ethylidene)-
hydrazono)methyl)-3-((Z)-((E)-(1-(4-(piperidin-4-yl)-
1H, H-5), 7.8 (d, J6′,5′/6′,5′ = 1.8 Hz, 2H, H-6′/6′), 7.6 (d, J4,5/6,5
=
8.7 Hz, 2H, H-4/6); EI-MS m/z (rel. int. %): 571 (M+, 42), 374
(89), 343 (100), 196 (37), 154 (61).
4,4'-(1E,1’E)-((2Z,2’E)-(1,3-Phenylenebis(methan-1-
yl-1-ylidene))bis(hydrazine-2,1-diylidene))bis(methan-1-yl-
1
1-ylidene)diphenol (6): Yield: 83 %; H NMR (DMSO-d6

Vol. 28, No. 1 (2016)
Synthesis and Antiurease & Antioxidant Activities of Bis-Schiff Bases of Isophthalaldehyde 41
phenyl)ethylidene)hydrazono)methyl)benzene (13): Yield:
84 %; H NMR (DMSO-d6 ppm): δ 8.8 (s, 1H, H-2), 8.5 (s,
RESULTS AND DISCUSSION
1
Schiff bases were synthesized by refluxing isophthalal-
dehyde with hydrazine hydrate in 1:2 in ethanol by refluxing
for 2-3 h. Reaction completion was monitored by TLC. After
completion of reaction the mixture was cooled, concentrated
and washed with n-hexane to obtain the pure product. This
product in second step is further reacted with different aromatic
aldehydes/acetophenone (1:2) in refluxing ethanol for 2-3 h.
Reaction completion was monitored by TLC. These Schiff
bases (1-16) were then washed with ethyl alcohol and n-hexane
to obtain pure products (Scheme-I, Table-1).
2H, H-7/7′), 8.0 (s, 2H, NH), 7.8 (d, J4,5/6,5 = 7.5 Hz, 2H, H-4/
6), 7.7 (d, J2′,3′/6′,5′/2′,3′/6′,5′ = 8.7 Hz, 4H, H-2′/6′/2′/6′), 7.6 (m,
1H, H-5), 6.9 (d, J3′,2′/5′,6′/3′,2′/5′,6′ = 8.4 Hz, 4H, H-3′/5′/3′/5′), 2.3
(s, 6H, CH3), 1.5 (s, 16H, H-pipridno); EI-MS m/z (rel. int.
%): 511 (M+, 42), 313 (100), 283 (69), 196 (23), 154 (44).
4-((E)-((Z)-(3-((E)-((Z)-((2,4 Dihydroxyphenyl)(phenyl)-
methylene)hydrazono)methyl) benzylidene)hydrazono)-
(phenyl)methyl)benzene-1,3-diol (14):Yield: 84 %; 1H NMR
(DMSO-d6 ppm): δ 12.2 (s, 2H, OH), 10.7 (s, 2H, OH), 7.6 (s,
2H, H-3′/3′), 7.5 (d, J,2′/3′/,6′,5′/2′,3′/6′,5′ = 2.4 Hz, 4H, H-2′/6′/2′/6′),
7.4 (m, 4H, H-3′/5′/3′/5′), 7.41 (s, 1H, H-2), 7.37 (d, 2H, J5′,6′/
5′,6′ = 8.4 Hz, H-5′/5′), 7.2 (d, J6′,5′/5′/6′,5′ = 8.4 Hz, 2H, H-6′/6′),
7.1 (m, 2H, H-4′/4′), 7.1 (m, 2H, H-4′/4′), 6.9 (d, J4,5/6,5 = 2.4
Hz, 2H, H-4/6), 6.35 (m, 1H, H-5); EI-MS m/z (rel. int. %):
511 (M+, 42), 313 (100), 283 (69), 196 (23), 154 (44).
CHO
H2N
NH2
Ethanol
NH2
NH2
N
N
N
OHC
2-3 h reflux
R1
N
R2
H2N
NH2
1-((E)-((E)-(Naphthalen-2-ylmethylene)hydrazono)-
methyl)-3-((Z)-((E)-(naphthalen-2-ylmethylene)hydra-
zono)methyl)benzene (15): Yield: 82 %; 1H NMR (DMSO-
d6 ppm): δ 8.4 (s, 4H, H-7/7′/2′/2′), 8.3 (s, 2H, H-8/8′/2), 8.2
(s, 1H, H-2), 8.1 (d, J = 6 Hz, 2H, H-4/6), 7.8 (m, 1H, H-5),
8.0 (d, J = 6.5 Hz, 6H, H-3′/3′/8′/8′/7′/7′), 7.9 (d, J5,6 = 7 Hz,
4H, H-4′/4′/6′/6′), 7.8 (m, 2H, H-5′/5′); EI-MS m/z (rel. int.
%): 438 (M+, 54), 416 (60), 365 (69), 289 (35), 156 (42).
2,2'-(1E,1’E)-((2Z,2’E)-(1,3-Phenylenebis(methan-1-
yl-1-ylidene))bis(hydrazine-2,1-diyli dene))bis(methan-1-
yl-1-ylidene)dibenzene-1,3-diol (16): Yield: 83 %; 1H NMR
(DMSO-d6 ppm): δ 11.2 (s, 2H, OH), 10.6 (s, 2H, OH), 7.6 (s,
2H, H-3′/3′), 7.5 (d, 4H, J,2′/3′/,6′,5′/2′,3′/6′,5′ = 2.4 Hz, 4H, H-2′/6′/
2′/6′), 7.43 (m, 4H, H-3′/5′/3′/5′), 7.41 (s, 1H, H-2), 7.37 (d,
R1
N
N
N
N
R1R2CO
R2
Ethanol
2-3 h
reflux
Scheme-I: Synthesis of bis-Schiff bases of isopthalaldehyde 1-16
TABLE-1
SYNTHESIZED BIS-SCHIFF BASE ANALOGS
OF ISOPTHALALDEHYDE (1-16)
Comp.
No.
Comp.
No.
R1
R2
H
R1
R2
CH3
1
9
OH
J5′,6′/5′,6′ = 8.4 Hz, 2H, H-5′/5′), 7.2 (d, J6′,5′/5′/6′,5′ = 8.4 Hz, 2H, H-
OH
6′/6′), 7.1 (m, 2H, H-4′/4′), 6.9 (d, J4,5/6,5 = 2.4 Hz, 2H, H-4/6),
6.35 (m, 1H, H-5), 1.8 (s, 6H, CH3); EI-MS m/z (rel. int. %):
541 (M+, 42), 413 (100), 383 (69), 186 (23), 144 (44).
Urease inhibition assay: Khan et al. [19] procedure was
followed for determining urease inhibition based on weather-
burn procedure [17]. 5 µL solution of sample was mixed with
25 µL of urease solution; mixture was incubated for 15 min at
30 °C. In 96 well plates the aliquots were mixed with sample
mixture of urea (100 mM) in buffer (40 µL) by re incubation.
To wells 70 µL of alkali reagent (0.5 % w/v sodium hydroxide
NaOH and 0.1 % sodium hypochlorate) and 50 µL of phenol
reagent (1 % w/v phenol and 0.005 % w/v sodium nitro-
prusside) were mixed.Against the blank increase in absorbance
was measured after 50 min at 630 nm. At pH 8.2 the reaction
mixture volume were 200 µL. Thiourea were used as positive
control. With help of formula the percentage inhibition were
measured. Measurement were done triplicate for accuracy.
Antioxidant assay: Zonia et al. [20] method was used
for measuring DPPH radical scavenging. In the ethanolic
solution of DPPH (1 mmol/L, 0.5 mL) 5mL ethanol sample
was added. At 30 °C the reaction mixtures were incubated for
0.5 h using UV-3000 spectrophotometer (Hitachi, Japan) the
absorbance was measured against ethanol. Using DPPH and
same amount of ethanol was used and measured on daily basis.
DPPH solution were prepared freshly and stored in aluminium
foiled flasks and measurements were done at dark at 4 °C. All
the measurement were done triplicate.
H
H
CH3
CH3
2
3
10
11
O2N
NO2
H3CO
HO
OH
OH
H
H
CH3
CH3
4
5
12
13
HO
OH
Cl
HO
OH
Cl
HN
H
H
C6H6
H
6
7
14
15
HO
HO
OH
NO2
OH
H
Me
8
16
H3CO
OCH3
OH

42 Rahim et al.
Asian J. Chem.
Urease inhibitory studies: Compounds 1-16 were subjected
Conclusion
for urease inhibition. Out of sixteen, only three compounds
showed potent inhibition. Compounds 4, 15 and 16 showed
an excellent urease inhibition with IC50 values 18.3 0.8, 13.8
0.4 and 13.9 0.2 µM respectively much better than the
standard inhibitor thiourea with IC50 value 21.8 0.11 µM
(Table-2). Compounds 4, 2,3,4-trihydroxy analog, 15 naphthyl
analog and 16 2,6-dihydroxy analog exhibit potent inhibition.
Compound 4 and 16 have hydroxyl group on phenyl ring.
Activity of compounds 4 and 16 might be attributed to hydroxyl
groups. This hydroxyl group might be involved in hydrogen
bonding with nickel of enzyme. Compound 15 have naphthalene
moiety, activity of compound might be due to arene interaction.
All other remaining compounds were found to be inactive.
In present work analogs 1-16 were synthesized and subjec-
ted to antiurease inhibition and antioxidant potential. Three
compounds showed potent urease inhibition and moderate anti-
oxidant activity. Analogs 4, 15 and 16 with IC50 values 18.3
0.8, 13.8 0.4 and 13.9 0.2 µM respectively were found
potent antiurease when compared with standard thiourea. The
same analogs also showed antioxidant potential with IC50
values, 19.663 0.8, 50.64 4.7 and 92.821 1.38 µM, respec-
tively as compared with standard quercitin.
ACKNOWLEDGEMENTS
The authors are grateful to Higher Education Commission
of Pakistan.
TABLE-2
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UREASE ACTIVITY OF BIS-SCHIFF BASES (1-16)
IC50 SEMa
(µ/M)
IC50 SEMa
(µ/M)
1. C.M. Collins and S.E.F. D’Orazio, Mol. Microbiol., 9, 907 (1993).
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Compounds
Compounds
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(2001).
N.A
N.A
N.A
18.3 0.8
N.A
N.A
N.A
N.A
21.8 .0.11
N.A
N.A
N.A
N.A
N.A
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
–
N.A
6. M. Lateef, L. Iqbal, N. Fatima, K. Siddiqui, N. Afza, U.M. Zia and A.
Mansoor, Pak. J. Pharm. Sci., 25, 99 (2012).
13.8 0.4
13.9 0.2
–
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Thioureac
SEMa is the standard error of the mean, NAb Not active, Thioureac is
standard inhibitor for urease inhibition
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Antioxidant activity: Compounds 1-16 were subjected
for DPPH radical scavenging activity. Out of sixteen, only
three compounds were active. Compounds 4, 15 and 16 showed
excellent to good DPPH radical scavenging activity with IC50
values 19.663 0.8, 50.64 4.7 and 92.821 1.38 µM, respec-
tively comparable to the standard inhibitor gallic acid with
IC50 value 23.436 0.43 µM (Table-3). Compounds 4, 2,3,4-
trihydroxy analog, 15 naphthyl analog and 16 2,6-dihydroxy
analog were active. Compound 4 and 16 have hydroxyl groups
on phenyl ring, activity might be due to these hydroxyl groups
which can stabilize the free radicals. Compound 15 has
naphthalene moiety, activity might due to areneinteraction.
Rests of the compound were not active against DPPH radical
scavenging.
TABLE-3
ANTIOXIDANT ACTIVITY OF BIS-SCHIFF BASES (1-16)
Compounds
IC50 SEMa
(µ/M)
Compounds
IC50 SEMa
(µ/M)
N.A
N.A
N.A
N.A
N.A
N.A
N.A
N.A
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
–
19.663 0.8
N.A
N.A
N.A
N.A
N.A
50.64 4.7
92.821 1.38
–
Gallic acid
23.436 0.43
SEMa is the standard error of the mean, NAb Not active, Gallic acid is
standard inhibitor for antioxidant inhibition