Synthesis, characterization and cytotoxicity of mixed ligand Mn(II), Co(II) and Ni(II) complexes

Article abstract of DOI:10.2298/JSC130813134O

Complexes of the type [ML'L(OH)(H₂O)], where M = Ni(II), Co(II) or Mn(II), L' = isatin and HL = 3-(2-phenylhydrazono)acetylacetone, 3-(2-(4- -chlorophenyl)hydrazono)acetylacetone or 3-(2-(4-bromophenyl)hydrazono)- acetylacetone, were synthesize

Full text of DOI:10.2298/JSC130813134O

J. Serb. Chem. Soc. 79 (8) 953–964 (2014)
JSCS–4639
UDC 546.712’732’742+547.442.3+
542.913:576+615.9
Original scientific paper
Synthesis, characterization and cytotoxicity of mixed ligand
Mn(II), Co(II) and Ni(II) complexes
1
2
1
SOUAD A. OSMAN , HANAN A. MOUSA , HISHAM ABDALLAH A. YOSEF ,
1
3
4
TAGHRID S. HAFEZ , ABDALLAH A. EL-SAWY , MOHAMED M. ABDALLAH
1
and ASHRAF S. HASSAN *
1
Department of Organometallic and Organometalloid Chemistry, National Research Centre,
2
El-Behoos Street, Dokki, P. O. Box 12622, Cairo, Egypt, Department of Inorganic
Chemistry, National Research Centre, El-Behoos Street, Dokki, P. O. Box 12622, Cairo,
3
Egypt, Chemistry Department, Faculty of Science, Benha University, Benha, Egypt and
4
Univet Pharmaceuticals Ltd, Balteem, Egypt
(
Received 13 August, revised 31 October, accepted 15 November 2013)
Abstract: Complexes of the type [ML′L(OH)(H O)], where M = Ni(II), Co(II)
2
or Mn(II), L′ = isatin and HL = 3-(2-phenylhydrazono)acetylacetone, 3-(2-(4-
-
chlorophenyl)hydrazono)acetylacetone or 3-(2-(4-bromophenyl)hydrazono)-
acetylacetone, were synthesized by equimolar reaction of a metal(II) chloride
with isatin and a 3-(2-arylhydrazono)acetylacetone. The resulting complexes
were characterized by elemental analyses, molar conductivity, spectral data (IR
and mass spectrometry) and magnetic moments. Furthermore, the ligands and
their metal complexes were screened for their cytotoxicity against different
human cancer cell lines using the sulforhodamine B (SRB) assay. The results
showed that most of the mixed ligand metal complexes have high cytotoxicity
in comparison with the reference drugs used.
Keywords: 3-(2-arylhydrazono)acetylacetone; isatin; transition metals; mixed
ligands; cytotoxicity.
INTRODUCTION
One of the main goals for research chemists and pharmacologists is the syn-
thesis of novel bioactive compounds for the development of better drugs to fight
diseases. Thus, coordination chemistry has developed very rapidly mainly in the
last 15 years since many ligands of no or low biological activity become more
1
,2
active when transferred to their metal complexes
increased activity when administered as metal complexes.
plexes containing heterocyclic ligands having nitrogen and/or sulfur have inc-
and some drugs show
3
–5
In addition, com-
*
Corresponding author. E-mail: Ashraf_salmoon@yahoo.com
doi: 10.2298/JSC130813134O
9
53
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9
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OSMAN et al.
reased biological activities compared to the original ligands.6,7 Recently, there is
an increasing interest in the synthesis of mixed ligand metal complexes due to
their biological significance. These complexes play important roles in biological
8
,9
processes since enzymes are known to be activated by metal ions. Moreover,
1
0
11
12,13
they have wide antituberculosis, antifungal, antibacterial and antitumor
pharmacological activities.
A literature survey reveals that isatin (indole-2,3-dione) and its derivatives
1
4
15
16,17
shows a wide range of antimicrobial, anticonvulsant, anticancer
and anti-
1
8
HIV activities. On the other hand, arylhydrazono-1,3-diketone derivatives have
been widely used as intermediates in the preparation of a large number of
biologically important heterocyclic compounds.
In view of these facts and continuing our interest in the synthesis of com-
1
9–21
2
2,23
pounds with promising biological activities,
Ni(II), Co(II) and Mn(II) com-
plexes of 3-(2-arylhydrazono)acetylacetone with isatin were prepared and charac-
terized by IR and UV–Vis spectroscopy, elemental analyses, molar conductivity
and magnetic susceptibility measurements. The study was extended to screen the
ligands and their metal complexes against different human cancer cell lines.
EXPERIMENTAL
Chemistry
All melting points were measured on a Gallenkamp melting point apparatus and are
uncorrected. The IR spectra were recorded (KBr disk) on a Perkin-Elmer 1650 FT-IR ins-
1
trument. The H-NMR (500 MHz) spectra were recorded on a Varian 500 MHz spectrometer
in DMSO-d using TMS as an internal standard. The FAB mass spectra of the complexes
6
were recorded on a JEOL JMS/AX-500 mass spectrometer. Elemental analyses were obtained
from the Micro Analytical Data Center at Cairo University, Egypt. The magnetic suscept-
ibilities were measured at 20 °C by the Gouy method at the Faculty of Science, Cairo Uni-
versity. The electronic absorption spectra were recorded on a PG Instruments Ltd., +80+
automatic UV–Vis spectrophotometer in DMSO. The molar conductance values of solutions
of the metal complexes in DMF (10- mol L ) were measured using Metrohem 660 con-
3
-1
ductivity meter.
Acetylacetone, p-chloroaniline, p-bromoaniline, aniline, sodium acetate, methanol and
hydrochloric acid were of Merck AR grade, Germany. Isatin was supplied by Riedel de Haën
AG, Germany. The employed NiCl ·6H O, CoCl ·6H O and MnCl ·4H O salts (Fluka, Ger-
2
2
2
2
2
2
many) were of AR grade.
Preparation of 3-(arylhydrazono)acetylacetones)
The 3-(arylhydrazono)acetylacetone derivatives (HL) were prepared by coupling acetyl-
acetone with different diazonium salts. Thus, a solution of acetylactone (0.01 mol) and sodium
acetate (5 g) in ethanol (50 mL) was cooled to 0–5 °C and then the diazonium salt (0.01 mol)
was added under stirring. The reaction was allowed to proceed at 0–5 °C for 30 min. The
3
-(arylhydrazono)acetylacetone derivatives were precipitated and collected by filtration,
2
4
washed with cold deionized water and recrystallized from ethanol.
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METAL COMPLEXES, SYNTHESIS AND CYTOTOXICITY
955
Preparation of the complexes 1–9
A solution of the metal chloride (3.4 mmol) in a minimum amount of water was added to
a hot solution of the mixed ligand (3.4 mmol) in methanol, whereby a clear solution was
obtained. The pH was increased from 6.0 to 8.0 with dilute NaOH solution. The mixture was
refluxed under stirring for 6 h. The formed complex was filtered off, washed several times
with hot methanol and dried under reduced pressure.
Biological experiments
In vitro cytotoxicity screening. The tested compounds were subjected to in vitro disease-
-
oriented primary antitumor screening. Different tumor cell lines were utilized. The human
tumor cell lines of the cancer screening panel were grown in RPMI 1640 medium containing 5 %
fetal bovine serum and 2 mM L-glutamine. In a typical screening experiment, 100 µL of cells
were inoculated into 96-well microtiter plates at plating densities ranging from 5000 to 40000
-
1
cells well , depending on the doubling time of the individual cell lines. After cell inoculation,
the microtiter plates were incubated at 37 °C, 5 % CO , 95 % air and 100 % relative humidity
2
for 24 h prior to the addition of the experimental drugs. After 24 h, two plates of each cell line
were also fixed in situ with trichloroacetic acid (TCA) to represent a measurement of the cell
population for each cell line at the time of drug addition (T ). Experimental drugs were
z
solubilized in DMSO at 400-fold of the desired final maximum test concentration and stored
frozen prior to use. At the time of drug addition, an aliquot of frozen concentrate was thawed
and diluted to 2-times the desired final maximum test concentration with complete medium
-
1
containing 50 µg ml gentamicin. Four additional 10-fold or 0.5log serial dilutions were made
to provide a total of five drug concentrations plus a control. Aliquots of 100 µL of these
different drug dilutions were added to the appropriate microtiter wells already containing 100
µL of medium, resulting in the required final drug concentrations. Following drug addition,
the plates were incubated for an additional 48 h at 37 °C, 5 % CO , 95 % air and 100 %
2
relative humidity. For adherent cells, the assay was terminated by the addition of cold TCA.
The cells were fixed in situ by the gentle addition of 50 µL of cold 50 % (w/V) TCA (final
concentration, 10 % TCA) and incubated for 60 min at 4 °C. The supernatant layer was
discarded and the plates were washed five times with tap water and air-dried. Sulforhodamine
B (SRB) solution (100 µL) at 0.4 % (w/V) in 1 % acetic acid was added to each well and the
plates were incubated for 10 min at room temperature. After staining, the unbound dye was
removed by washing five times with 1 % acetic acid and the plates were air dried. The bound
®
stain was subsequently solubilized with 10 mM Trizma base and the absorbance was read on
an automated plate reader at a wavelength of 515 nm. For suspension cells, the methodology
was the same except that the assay was terminated by fixing the settled cells at the bottom of
the wells by gently adding 50 µL of 80 % TCA (final concentration, 16 % TCA). The
parameter IC50 which is the concentration of the drugs inducing a 50% inhibition of cell
2
5-27
growth of treated cells when compared to the growth of control cells.
RESULTS AND DISCUSSION
Chemistry
The ligands. The 3-(arylhydrazono)acetylacetone derivatives (HL) are pre-
pared via coupling between diazotized aromatic amine derivatives and acetyl-
2
4
acetone in a 1:1 molar ratio according to Scheme 1. The structures of these
ligands were confirmed by elemental analyses and their spectral data (IR and
1
H-NMR), which are discussed later with their metal complexes.
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9
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OSMAN et al.
Scheme 1. Synthesis of 3-(arylhydrazono)acetylacetone derivatives (HL).
The complexes. Reactions of the hydrated metal(II) chloride with 3-(arylhyd-
razono)acetylacetone and isatin in equimolar ratios resulted in formation of the
complexes 1–9, shown in Scheme 2.
The physical, analytic and spectral data for the ligand and their metal
complexes are given in the Supplementary material to this paper.
Infrared spectra of the ligands and their complexes
1
2
3
In the infrared spectra of the ligands (HL , HL and HL ), the broad band in
–
1
the range 3428–3086 cm indicates the existence of strong intramolecular hyd-
rogen bonding. Furthermore, there are two strong bands at 1673 and 1623 cm–1
28
assignable to ν(C=O, free) and ν(C=O, hydrogen bonded), respectively. The
–
1
ν(C=N) band appears at 1593 cm , which remains almost unaffected in the
spectra of all the complexes suggesting that the nitrogen atom is not involved in
–
1
the coordination, while the ν(C=O) band at 1623 cm is shifted to lower fre-
quencies in the spectra of the complexes, suggesting that this oxygen atom is
–
1
involved in the coordination, while the carbonyl group at ≈1673 cm remains
–
1
almost unchanged in the spectra. The prominent band present at ≈1518 cm of
the ligands is due to δ(N–H) vibrations, which disappears in the spectra of all the
complexes because of the replacement of the hydrazone NH proton with a metal
ion. The infrared spectrum of isatin (L′) shows a band at 3191 due to ν(N–H) and
–
1
two ν(C=O) group absorptions at 1745 and 1731 cm . The IR spectra of the
complexes show that the two carbonyl groups of isatin ligand are shifted to lower
frequency, suggesting that both groups are involved in the coordination, while
–
1
ν(N–H) at 3191 cm is not changed, indicating that the (N–H) group is not
involved in the coordination.
Conclusive evidence of bonding was also given by the observation that new
bands in the spectra of all metal complexes 1–9 appear in the low frequency
–
1
regions at 493–438 and 584–540 cm characteristic of ν(M–O) and ν(M–N)
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METAL COMPLEXES, SYNTHESIS AND CYTOTOXICITY
957
2
9
stretching vibrations, respectively. Furthermore, the observed broad band at
–
1
3
550 cm in all complexes were attributed to the OH group and the OH stretch-
1
0
ing vibrations of lattice water molecules.
Scheme 2. Synthesis of mixed ligand complexes of the type [ML′L(OH)(H O)].
2
Nuclear magnetic resonance of the ligands
1
The H-NMR spectrum of HL revealed a single proton at δ ≈14.02 ppm due
…
30,31
1
2
to the N–H O=C group.
The H-NMR spectrum of HL is illustrated in
Fig. S-1 of the Supplementary material to this paper.
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OSMAN et al.
Mass spectra of the complexes
The molecular ion peaks in the mass spectra of some complexes were used
to confirm the molecular formula. Thus, the mass spectra of the Ni(II) complexes
1
confirmed the molecular formulas, e.g., [NiL′L (OH)(H O)] and
2
3
[
NiL′L (OH)(H O)] confirmed C H N NiO and C H BrN NiO , respect-
2
19 19
3
6
19 18
3
6
ively. Similarly, the mass spectra of the Co(II) complexes confirmed the mole-
2
3
cular formulas, e.g., [CoL′L (OH)(H O)] and [CoL′L (OH)(H O)] confirmed the
2
2
molecular formulas C H ClCoN O and C H BrCoN O , respectively.
1
9
18
3
6
19 18
3 6
3
Moreover, the mass spectrum of the Mn(II) complex, e.g., [MnL′L (OH)(H O)]
2
confirmed the molecular formula C H BrMnN O .
1
9
18
3 6
Electronic spectra and magnetic moments
1
2
3
The UV–visible spectra of the free ligands HL , HL , HL and L′ showed
absorption bands at 292–297 and 418–440 nm due to π→π* and n→π* trans-
itions, respectively. These bands were blue- or red-shifted in the spectra of the
complexes due to coordination in the ligands.
The Mn(II) complexes 3, 6 and 9 exhibited two weak bands at 618–622 and
6
4
4
6
4
4
5
20–526 nm which were attributed to A → T ( G) and A → T ( G)
1g 1g 1g 2g
transitions, respectively. These absorptions are consistent with an octahedral geo-
metry around the Mn(II) atom. The magnetic moment values of the Mn(II) com-
plexes were in the range of 5.82–5.90 μ , corresponding to five unpaired elec-
B
3
3
trons, which is also indicative of octahedral geometry.
The electronic spectra of the Co(II) complexes 5 and 8 showed two d–d
4
4
transitions in the ranges 654–661 and 540–548 nm due to the T (F) → A (F)
1
g
2g
4
4
and T (F) → A (p) transitions, respectively, indicating an octahedral con-
1
g
2g
4
4
figuration around the Co(II) atom. The T (F) → T (F) transition (1237–1242
2
g
1g
nm) would be observed in the near IR region. This region was out the range of
3
4
the employed spectrophotometer. The µeff values for the Co(II) complexes
were in the range 4.87–4.94 μ , which are similar to those reported for octa-
B
3
5
hedral Co(II).
The Ni(II) complexes 1, 4 and 7 exhibited two absorption bands in the
3
3
ranges 963–988 and 572–581 nm, which are assigned to A (F) → T (F) and
2
g
2g
3
3
A (F) → T (F) transitions, respectively. However, the absorption bands at
2
g
1g
3
3
4
20–422 nm due to A (F) → T (p) was overlapped with the ligand absorp-
2g 1g
tion bands. The spectra of these complexes support an octahedral stereochemistry
around the Ni(II) atom. The room temperature magnetic moment values of the
Ni(II) complexes were 3.17–3.20 μ , which are in the normal range observed for
B
3
6
octahedral Ni(II) complexes.
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METAL COMPLEXES, SYNTHESIS AND CYTOTOXICITY
959
Molar conductance measurements
The molar conductivities of 10–3 mol L–1 solutions of the complexes in
DMF were measured at room temperature. The results were in the range 22.1–
–
1
2
–1
–
11.6 Ω cm mol , indicating that all the metal complexes had molar con-
3
7
ductance values in the range characteristic for non-electrolytes.
Biological activity
In vitro cytotoxicity screening. The cytotoxicities of the mixed ligand com-
1
3
plexes [ML′L(OH)(H O)], the ligands HL –HL and L′ were determined using
2
the SRB assay on different human cancer cell lines including: cervical carcinoma
(
KB), ovarial carcinoma (SK OV-3), CNS cancer (SF-268), non-small cell lung
cancer (NCl H460), colon adenocarcinoma (RKOP 27) (Table I), anti-leukemia
(
(
HL60, U937, K562), melanoma (G361, SK-MEL-28) and neuroblastoma
GOTO, NB-1) (Table II). The cytotoxic effect of the ligands and their metal
complexes [ML′L(OH)(H O)] on the cell lines HeLa (cervical), MCF-7 (breast),
2
HT1080 (fibrosarcoma) and HepG2 (liver) were also tested (Table III). The
results are expressed as the IC , which is the concentration of a drug that causes
5
0
a 50 % reduction in the proliferation of cancer cells when compared to the
growth of the control cells.
TABLE I. Cytotoxicity (IC50 / nM, the concentration required for 50 % inhibition of cell
growth) of the ligands and the mixed ligand complexes determined by using SRB assay on
different human cancer cell lines; the values for most potent compound are marked by “*”
The ligands and their
metal complexes
Cell line
KB
4.40
6.70
0.32*
4.40
5.60
9.80
0.55
0.45
0.45
0.65
8.00
0.67
0.90
4.46
–
SK OV-3
5.40
5.46
3.20
3.40
6.70
8.80
0.55*
8.80
7.60
0.67
7.70
5.60
0.89
–
SF-268
4.50
0.35*
0.55
3.50
0.43
9.90
5.60
0.50
0.40
4.50
0.75
0.65
0.85
–
NCI H460
0.65
0.89
0.44
0.40*
0.56
0.68
0.66
0.43
0.67
0.87
0.57
0.43
0.84
–
RKOP27
7.50
2.30*
4.30
5.50
7.60
4.50
7.80
8.80
6.40
4.80
4.30
4.50
2.30*
–
L′
HL
1
1
2
3
2
HL
4
5
6
3
HL
7
8
9
Fluorouracil
Doxorubicin
Cytarabine
Gemcitabine HCl
Capecitabine
4.16
–
–
–
7.68
–
–
–
–
–
–
–
–
2.13
–
–
4.33
–
–
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OSMAN et al.
TABLE II. Cytotoxicity (IC50 / nM, the concentration required for 50 % inhibition of cell
growth) of the ligands and the mixed ligand complexes determined by using SRB assay on
different human cancer cell lines; the values for most potent compound are marked by “*”
Cell line
The ligands and their
metal complexes
Leukemia
Melanoma
Neuroblastoma
HL60
8.00
6.50
0.75
5.30
3.40
6.00
0.44
0.56
0.32*
0.67
8.00
0.33
0.80
1.13
–
U937 K562 G361 SK-MEL-28 GOTO NB-1
L′
HL
6.80
7.70
9.00
5.40
7.30
8.70
0.65
3.50
6.00
0.43*
6.30
8.00
0.79
4.45
–
3.70 0.43*
5.00
4.00
4.00
5.00
1.00*
8.00
4.00
6.00
8.00
7.00
8.00
7.00
8.00
–
0.65
3.00
6.80
5.87
7.60
7.50
0.57
0.68
0.67
4.80
3.60
9.87
3.00
4.00
2.30
0.70
0.69
0.56
1
0.87
0.60
5.40
0.60
9.00
6.00
0.68
0.90
6.40
0.87
0.57
0.77
0.88
0.50
8.80
0.64
0.59
0.54
1
2
3
2
HL
4
5
6
3
HL
4.70 0.36*
0.50 7.60
0.34* 9.00
7
8
9
0.40* 0.70
0.50
8.00
6.66
–
0.70
0.60
–
0.56
4.73
–
0.65
5.15
–
Doxorubicin
Aldesleukin
6.66
3.45
TABLE III. Cytotoxicity (IC50 / nM, the concentration required for 50 % inhibition of cell
growth) of the ligands and the mixed ligand complexes determined by using SRB assay on
different human cancer cell lines; the values for most potent compound are marked by “*”
Cell line
The ligands and their
HeLa
cervical)
0.449
9.860
0.009*
7.680
0.897
6.600
0.780
5.640
0.600
0.960
6.500
0.770
0.444
0.114
MCF-7
(breast)
3.650
0.790
9.600
8.400
4.587
7.600
0.900
4.970
0.764
5.800
9.600
4.600
0.760*
0.155
HT1080
(fibrosarcoma)
7.86
HepG2
(liver)
2.30
0.64
0.80
0.79
0.47
3.64
0.77
0.91
0.89
0.54*
8.50
0.79
6.50
1.31
metal complexes
(
L′
HL
1
0.45
0.09*
8.69
0.54
5.80
3.65
0.99
0.87
2.50
0.86
7.00
0.59
1.16
1
2
3
2
HL
4
5
6
3
HL
7
8
9
Tamoxifen
Screening the cytotoxicity of the mixed ligand complexes [ML′L(OH)(H O)]
2
1
2
3
and the ligands HL , HL , HL and L′ on cervical carcinoma (KB), where 5-fluo-
rouracil was used as a standard drug (IC = 4.46 nM), shows that the complexes
, 4, 5, 6, 8, and 9, and the ligand HL were more potent than the standard drug.
5
0
3
1
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METAL COMPLEXES, SYNTHESIS AND CYTOTOXICITY
961
In the case of the ovarial carcinoma (SK OV-3) cell line, the tested com-
3
plexes 4 and 9 and the ligand HL (IC = 0.55, 0.89 and 0.67 nM, respectively)
5
0
were found to be more potent than the standard drug doxorubicin (IC50 = 4.16 nM).
Studying the cytotoxicity of the tested complexes and the ligands on the
CNS cancer (SF-268) cell line using cytarabine (IC50 = 7.68 nM) as a standard
2
drug, reveals that all the tested complexes and the ligands except HL (IC50
=
=
9.90 nM) were more potent than the standard drug.
In the case of the non-small cell lung cancer (NCl H460) cell line, all of the
tested complexes and the ligands were found to be more potent than the standard
drug gencitabine hydrochloride (IC50 = 2.13 nM).
In the case of the colon adenocarcinoma (RKOP 27) cell line, the ligand HL1
and the complex 9 (IC50 = 2.30 nM) were found to be more potent than the
standard drug capecitabine (IC50 = 4.33 nM).
The study of the cytotoxicity on the leukemia (HL60) cell line indicated that
1
2
the ligands L′, HL , HL and the complexes 2, 3 and 7 were less potent com-
pounds than doxorubicin (IC50 = 1.13 nM).
3
In the case of the leukemia (U937) cell line, the ligand HL (IC = 0.43
5
0
nM) was the most potent, while complex 1 (IC50 = 9.00 nM) was the least bio-
active.
In the case of the leukemia (K562) cell line, the tested complexes and the
2
ligands, except ligand HL and complex 9, were more active than the standard
3
drug doxorubicin (IC50 = 6.66 nM); the ligand HL and complex 4 had activity
comparable to that of doxorubicin.
On estimation of the cytotoxicity on the melanoma (G361) cell line, the
tested complexes and the ligands, expect complex 4 (IC50 = 8.80 nM) were more
active than the standard drug aldesleukin (IC50 = 6.66 nM).
In the case of the melanoma (SK-MEL-28) cell line, the tested complexes
and the ligands were less active than the standard drug Aldesleukin (IC50 = 3.45
nM), expect complex 3 that was more active (IC50 = 1.00 nM)
Cytotoxicity of the tested complexes and the ligands on neuroblastoma
(
GOTO) cell line showed that complex 8 was the most potent (IC50 = 0.34 nM)
and more active than the standard drug doxorubicin (IC50 = 4.73 nM).
In the case of the neuroblastoma (NB-1) cell line, complex 2 was less active
3
than the standard drug doxorubicin (IC50 = 5.15 nM), while ligand HL (IC
=
50
=
0.36 nM) was the most active.
The cytotoxicity of the tested complexes and the ligands on the HeLa (cer-
vical) cell line showed that complex 1 (IC50 = 0.009 nM) was the most potent
and more active than the standard drug tamoxifen (IC50 = 0.114 nM).
In the case of the MCF-7 (breast) cell line, the standard drug tamoxifen (IC50
=
=
0.155 nM) was more active than all the other tested complexes and ligands.
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OSMAN et al.
In the case of the HT1080 (fibrosarcoma) cell line, complex 1 (IC50 = 0.09
nM) was the most potent and complex 2 (IC50 = 8.69 nM) was found to be less
potent than tamoxifen (IC50 = 1.16 nM).
The cytotoxicity of the tested complexes and the ligands on the HepG2
3
(
liver) cell line shows that the complexes 1–6 and 8, and the ligands HL and
1
HL were more active than the standard drug tamoxifen (IC = 1.16 nM),
5
0
whereby complex 3 (IC50 = 0.47 nM) was the most promising one.
CONCLUSIONS
Ni(II), Co(II) and Mn(II) complexes of 3-(2-arylhydrazono)acetylacetone
1
3
(
HL) and isatin (L′) were synthesized. The ligands (L′ and HL –HL ) act as
bidentate molecules, whereby L′ was coordinated through two oxygen atoms
while the 3-(2-arylhydrazono)acetylacetones were coordinated by oxygen and
nitrogen atoms. The prepared complexes 1–9, which were non-electrolytes, have
octahedral geometry with the general structural formula [ML′L(OH)(H O)]. The
2
cytotoxicity results of the ligands and their complexes 1–9 against different
human cancer cell lines indicated that most of the complexes exhibited high cyto-
toxicity at very low concentrations in comparison with the reference drugs con-
sidered.
SUPPLEMENTARY MATERIAL
Physical, analytic and spectral data of the ligands and complexes are available elec-
tronically at http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
И З В О Д
СИНТЕЗА, КАРАКТЕРИЗАЦИЈА И ЦИТОТОКСИЧНА АКТИВНОСТ КОМПЛЕКСА
МАНГАНА(II), КОБАЛТА(II) И НИКЛА(II) СА МЕШОВИТИМ ЛИГАНДИМА
1
2
1
1
SOUAD A. OSMAN , HANAN A. MOUSA , HISHAM ABDALLAH A. YOSEF , TAGHRID S. HAFEZ , ABDALLAH A.
3
4
1
EL-SAWY , MOHAMED M. ABDALLAH и ASHRAF S. HASSAN
1
Department of Organometallic and Organometalloid Chemistry, National Research Centre, El-Behoos Street,
2
Dokki, P. O Box 12622, Cairo, Egypt, Department of Inorganic Chemistry, National Research Centre, El-
3
Behoos Street, Dokki, P. O. Box 12622, Cairo, Egypt, Chemistry Department, Faculty of Science, Benha
4
University, Benha, Egypt и Univet Pharmaceuticals Ltd, Balteem, Egypt
У реакцијама одговарајућег метал(II)-хлорида са изатином и 3-(2-арилхидразо-
но)ацетилацетоном синтетизовани су комплекси опште формуле [ML′L(OH)(H O)] (где
2
је М = Ni(II), Co(II) или Mn(II), L′ = изатин и HL = 3-(2-фенилхидразоно)ацетилацетон,
3-(2-(4-хлорфенил)хидразоно)aцетилацетон или 3-(2-(4-бромфенил)хидразоно)aце-
тилацетон). Комплекси су окарактерисани применом елементалне микроанализе, спек-
троскопских метода (IR спектроскопија и масена спектрометрија) и мерењем моларне
проводљивости и магнетног момента. Испитивана је цитотоксична активност лиганда и
комплекса на различитим туморским ћелијским линијама применом SRB теста.
Добијени резултати су показали да већина комплекса показује већу цитотоксичну
активност у поређењу са стандардним лековима.
(
Примљено 13. августа, ревидирано 31. октобра, прихваћено 15. новембра 2013)
Available on line at www.shd.org.rs/JSCS/
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METAL COMPLEXES, SYNTHESIS AND CYTOTOXICITY
963
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