Synthesis and biological activity of novel heavy metal complexes of 5-amino-1, 10-phenanthroline and 1,10-phenanthroline

Article abstract of DOI:10.2478/s11532-012-0046-x

Novel heavy metal complexes: Sr(5-NH₂-phen)₄(NO ₃)(OH)(H₂O)₂ (1) (synthesized via a static self-assembly process) and Sn(phen) (NO₃)(OH)(H₂O) (2), Sn(5-NH₂-phen)(OH)(Cl)(H₂O) (3), Pb(5-NH ₂-phen)(NO₃)₂(H₂O) (4) (obtained via metal competitive reactions under mild conditions) were reported. The coordination compounds were characterized by elemental analysis, FTIR-spectroscopy and FAB-mass spectrometry. Their cytotoxicity was measured by MTS-test towards human tumour (MDA-MB-231, HT-29, HeLa, HepG2) and non-tumour diploid (Lep-3) cell lines. The most pronounced cytotoxic effect on all cancer lines showed 1 and 4 at their high concentrations as well as 1 at its lower ones (≤ 4×10^-2 mg). Therefore, strontium complex of 5-amino-o-phenanthroline (1) exhibited the widest antitumour spectrum activity, having no toxicity to non-tumour cells at quantities ≤ 4×10 ^-2 mg. The computed EC₅₀ values of 1-4 against MDA-MB-231, HT-29, HeLa, HepG2 varied from 1.40×10^-3 to 6.31×10 ^-6 M. Towards Lep-3 substances 2-4 showed IC₅₀ 7.52×10^-4 - 0.44 M. Substance 1 possess EC₅₀=1. 26×10^-7 M to the non-tumour cells. Versita Sp. z o.o.

Full text of DOI:10.2478/s11532-012-0046-x

Cent. Eur. J. Chem. • 10(4) • 2012 • 1034-1041
DOI: 10.2478/s11532-012-0046-x
Central European Journal of Chemistry
Synthesis and biological activity of novel
heavy metal complexes of 5-amino-1,
0-phenanthroline and 1,10-phenanthroline
1
Short Communication
1
*
1
Nikolay Kaloyanov , Mihail Neykov ,
2
1
Diana W. Wesselinova , Georgi D. Dimitrov
1Department of Organic Chemistry,
University of Chemical Technology
and Metallurgy, Sofia 1756, Bulgaria
2Institute of Experimental Morphology,
Pathology and Anthropology with Muzeum,
Bulgarian Academy of Sciences, Sofia 1113, Bulgaria
Received 25 January 2012; Accepted 17 March 2012
Abstract: Novel heavy metal complexes: Sr(5-NH -phen) (NO )(OH)(H O) (1) (synthesized via a static self-assembly process) and Sn(phen)
2
4
3
2
2
(
NO )(OH)(H O) (2), Sn(5-NH -phen)(OH)(Cl)(H O) (3), Pb(5-NH -phen)(NO ) (H O) (4) (obtained via metal competitive reactions
3 2 2 2 2 3 2 2
under mild conditions) were reported. The coordination compounds were characterized by elemental analysis, FTIR-spectroscopy
and FAB-mass spectrometry. Their cytotoxicity was measured by MTS-test towards human tumour (MDA-MB-231, HT-29, HeLa,
HepG2) and non-tumour diploid (Lep-3) cell lines. The most pronounced cytotoxic effect on all cancer lines showed 1 and 4 at their
-
2
high concentrations as well as 1 at its lower ones (≤ 4×10 mg). Therefore, strontium complex of 5-amino-o-phenanthroline (1)
-
2
exhibited the widest antitumour spectrum activity, having no toxicity to non-tumour cells at quantities ≤ 4×10 mg. The computed
-
3
-6
EC50 values of 1-4 against MDA-MB-231, HT-29, HeLa, HepG2 varied from 1.40×10 to 6.31×10 M. Towards Lep-3 substances
-
4
-7
2
-4 showed IC50 7.52×10 - 0.44 M. Substance 1 possess EC =1.26×10 M to the non-tumour cells.
50
Keywords: Metal complexes • Self-assembly • 5-amino-1,10-phenanthroline • 1,10-phenanthroline• Cytotoxic activity
Versita Sp. z o.o.
©
1. Introduction
variety of topologies and shapes have been constructed
in this way including boxes, microcycles, helicates and
Recently there has been a growing interest on the others [1,2].
preparation and characterization of coordination
However, there are almost no data on the synthesis
compounds with various organic ligands. Some and biological activity of complexes of 5-amino-1,10-
medicines and many other biologically active substances phenanthroline (5-NH -phen) with alkaline earth and
2
(e.g. enzymes, hormones, hemoglobin, chlorophyll, etc.) heavy metals, while there are some publications
belong to this group.
concerning coordination compounds of 1,10-
One of the most promising approaches to the phenanthroline (phen). Metal complexes with the
generation of complex supramolecular architectures following structure are described: [MeEtSn]Cl (phen)
2
2
is metal-driven self-assembly. They are prepared [3], (phenH)[SnFS ].xH O [4], [Pb(phen) (iso-Bu PS ) ]
2
2
2
2
2 2
when metal-coordinated building blocks interact [5], [Pb (bta) (phen) ].2H O, where(H bta)isN,N-bis[1(2)
2
2
2
2
2
spontaneously with bridging units which are connected H-tetrazol-5-yl]amine [6]. Some other coordination
by weak non-covalent bonds. Molecules with a wide compounds - [Ca(PDALC) ](ClO ) and [Pb(PDALC)
2
4 2
*
E-mail: nikolaykaloyanov@yahoo.com
1034

N. Kaloyanov et al.
(
ClO ) ], where (PDALC) is 2,9-bis(hydroxymethyl)- be synthesized. Their citotoxicity towards some human
4 2
phen are reported as well [7]. Their crystal structures tumour cell lines also will be tested.
were solved by X-ray diffraction.
In our previous investigations, we reported on
the synthesis, characterization and crystal structure 2. Experimental procedure
of complexes of alkaline earth metal ions with phen.
Under specific mild conditions, via self-assembly 2.1. Chemistry
processes, we obtained the following complexes: A novel coordination compound of heavy alkaline earth
Mg(phen) (NO ) (H O) [8], [Ca(phen) (H O) (NO )]NO
metal (Sr) with 5-amino-1,10-phenanthroline with a
9] and Ba(phen) (NO ) (H O) [10]. The X-ray diffraction composition Sr(5-NH -phen) (NO )(OH)(H O) (1) was
3
3
2
2
9
2
2
2
3
3
[
2
3
2
2
2
2
4
3
2
2
analysis revealed that in the calcium complex only one synthesized via a static self-assembly process. This is
of the nitrate anion is coordinated to the metal ion, while possible due to weak interactions between an organic
2
another is in the outer shell [9]. We also described the ligand and metal having s -electron configuration. To
synthesis of some metal complexes of phen as well as obtain other three new complexes: Sn(phen)(NO3)
of 5-NH -phen with composition: Pd(phen) (H O)(NO )
(OH)(H O) (2), Sn(5-NH -phen)(OH)(Cl)(H O) (3) and
2
2
2
3
2
2
2
2
[
11] and Pd(5-NH -phen) (NO ) [12]. It is noteworthy to Pb(5-NH -phen)(NO ) (H O) (4), competitive reactions
2 2 3 2
2 3 2 2
2
+
2+
mention the various biological activity of the resulting betweenheavymetalcations(Sn andPb ),possessing
complexes. Coordination compounds of alkaline earth a p -electron configuration, and Ca in a water-alcohol
2
2+
metals (Mg, Ca, Ba) with phen and their palladium(II) solution at the presence of phen or 5-NH -phen were
2
analogue show high antibacterial activity, especially conducted.
against Escherichia coli. Moreover, they have no
acute toxicity when administered intraperitoneally
(
i.p.) in rats at doses up to 10 mg [11]. The complex
N
N
Pd(5-NH -phen) (NO ) possesses strong anticancer
activity against a 100% lethal myeloid subcutaneous
tumour in hamsters.
2
2
3 2
On the other hand, its phen analogue
-
Pd(phen) (H O)(NO ) did not reveal any antitumour
2
2
3 2
activity [12]. This led us to obtain and study the
anticancer activity of other heavy metal complexes with
5
-NH -phen. It should be noted that compounds Pd(5-
1,10-phenanthroline (phen)
2
NH -phen) (NO ) and Pd(phen) (NO ) (H O) did not
2
2
3
2
2
3
2
2
show any histological alterations in the observed lung,
liver, spleen and lymph nodes of White Wistar rats as
well as any cytotoxic effect. The tests for immunological
response predominantly showed stimulation of the
antibody-producing B-cells [13]. Some new molecular
complexes of phen with aromatic heterocycles also
showed well expressed anticancer activity and lack of
toxicity towards non-tumour cells [14].
N
H N
2
N
The synthesis of mixed-ligand complexes of
palladium(II) with phen and 5-NO -phen, possessing
5-amino-1,10-phenanthroline (5-NH -phen)
2
2
antitumour activity, have been described [15,16]. Narla
et al. [17] reported on anticancer agent containing The synthesized compounds were characterized by
vanadium and 4,7-dimethyl-phen (Me -phen) with the elemental analysis, FTIR-spectroscopy and FAB-mass
2
formula VO(Me -phen) .
spectrometry.
2
2
Aim of the present study is the obtaining of a new
coordinationcompoundoftheheavyalkalineearthmetal 2.1.1. Chemicals and apparatus
Sr) with a rarely used ligand 5-NH -phen throughout 1,10-Phenanthroline.H O, Ca(NO ) •4H O, Sr(NO ) ,
(
2
2
3
2
2
3 2
a self-assembly process. Via competitive reactions SnCl •2H O and Pb(CH COO) •3H O were obtained
2
2
3
2
2
between heavy (Sn and Pb) and alkaline earth (Ca) from Merck, Darmstadt. 5-Amino-1,10-phenanthroline.
metals, novel complexes of phen and 5-NH -phen will H O was prepared in our laboratory from
2
2
1035

Synthesis and biological activity of novel heavy metal complexes
of 5-amino-1,10-phenanthroline and 1,10-phenanthroline
5
-nitro-1,10-phenanthroline by reduction with hydrazine solution was hot filtered, cooled to room temperature
hydrate using Raney-nickel as a catalyst. All other and water added to 25 mL. The filtrate stayed
chemicals used were of the highest available quality. in a refrigerator at 2–3°C for one week. Amorphous
Composition of the products was determined by yellow
elemental analysis on a VarioEl (Elemental analysen washed with cold distilled water and ether,
systeme GmbH). FAB-mass spectra were taken on a and dried in desiccator over P O .
VG autospec mass spectrometer. The samples were Yield: 0.065 g.
dissolved in NBA and lactic acid. Infrared spectra Anal. calcd. for C H N O ClSn (C, H, N): Calculated
were recorded on a Perkin-Elmer 1600 Series FTIR (%): C, 37.49; H, 3.12; N, 10.93. Found (%): C, 37.89; H,
residue
formed,
were
filtered
off,
a
4
10
12
12
3
2
−
1
-1
spectrophotometer in the range of 4400–450 cm , 2.72; N, 11.26. FTIR (cm ): 3404, 3324, 3225, 1638,
−1
+
resolution 4 cm , in KBr pellets.
1516. FAB-mass (m/z): 154 (SnCl) , 196 (5-NH -phen).
2
+
+
+
H , 385 Sn(5-NH -phen).H Cl , 391 (5-NH -phen) .H ,
2
2
2
2
+
2
0
0
.1.2. Synthesis of Sr(5-NH -phen) (NO )(OH)(H O) (1) 413 (5-NH -phen) .Na .
.096g(0.450mmol)5-amino-1,10-phenanthroline•H O,
.355 g (1.677 mmol) Sr(NO ) and 2.5 mL of 96% 2.1.5. Synthesis of Pb(5-NH -phen)(NO ) (H O) (4)
2 4 3 2 2
2
2
2
3
2
2
3
2
2
ethanol were dissolved in 20 mL distilled water at 0.096g(0.450mmol)5-amino-1,10-phenanthroline•H O,
2
70°С. The solution was hot filtered, cooled to room 0.148
g (0.627 mmol) Ca(NO ) •4H O, 0.237 g
3 2 2
temperature and water was added to 25 mL. The filtrate (0.625 mmol) Pb(CH COO) •3H O and 2.5 mL of
3
2
2
stayed in a refrigerator at 2–3°C for one month. Yellow 96% ethanol were dissolved in 20 mL distilled water
crystals formed, filtered off, washed with cold distilled at 70°С. The mixture was hot filtered, cooled to room
water and dried in a desiccator over P O . Yield: temperature and water added to 25 mL. The filtrate
4
10
0.052 g.
stayed in a refrigerator at 2–3°C for one week. Yellow
Anal. calcd. for C H N O Sr (C, H, N): Calculated crystals formed, were filtered off, washed with cold
4
8
41 13
6
(
%): C, 58.56; H, 4.16; N, 18.50. Found (%): C, 58.70; distilled water and dried in a desiccator over P O .
4 10
-1
H, 4.57; N, 18.53. FTIR (cm ): 3440, 3350, 3226, 1636, Yield: 0.099 g.
513, 1384, 824. FAB-mass (m/z): 196 (5-NH -phen). Anal. calcd. for C H N O Pb (C, H, N):
1
2
12 11
4
7
+
+
+
H , 391 (5-NH -phen) .H , 413 (5-NH -phen) .Na , 476 Calculated (%): C, 46.38; H, 2.89; N, 18.03. Found (%):
2
2
2
2
+
+
-1
[
Sr(5-NH -phen) -H ] .
C, 46.43; H, 2.87; N, 17.79. FTIR (cm ): 3430, 3342,
227, 1635, 1515, 1362, 822. FAB-mass (m/z): 196
2
2
3
+
+
2
0
0
.1.3. Synthesis of Sn(phen)(NO )(OH)(H O) (2)
(5-NH -phen).H , 465 [Pb(5-NH -phen) (NO )] , 660
2 2 3
3
2
+
.386
g
(1.950 mmol) 1,10-phenanthroline•H O, [Pb(5-NH -phen) (NO )] .
2 2 2 3
.519
g
(2.301 mmol) SnCl •2H O, 0.590
g
2
2
(
2.498 mmol) Ca(NO ) •4H O and 10 mL of 96% 2.2. Citotoxicity assays
3
2
2
ethanol were diluted in 80 mL distilled water at 70°С for The cytotoxicity of the substances was measured
0 min. The solution was hot filtered, cooled to in vitro using the cultivated human tumour
3
room temperature and water added to 100 mL. cell lines: epithelial colorectal carcinoma HT-29,
The filtrate stayed in a refrigerator at 2–3°C for breast cancer epithelial-like morphology MDA-
24
h. Amorphous yellow residue formed was MB-231, epithelial cervix adenocarcinoma HeLa,
filtered off, washed with cold distilled water, diethyl hepatocellular carcinoma liver HepG2 and non-tumour
ether and dried in a desiccator over P O . Yield: diploid cell line Lep-3 (as a control). Compounds 1, 2,
4
10
0.137 g.
3 and 4 were evaluated for their cytotoxicity in vitro,
Anal. calcd. for C H N O Sn (C, H, N): Calculated towards the following cultivated human tumour and
12
11
3
5
(
%): C, 36.32; H, 2.78; N, 10.60. Found (%): C, 36.21; non-tumour cell lines, using MTS-test [18]:
-1
H, 2.85; N, 10.54. FTIR (cm ): 3490, 3327, 1519, 1385,
8
H .2H O, 235 (phen).H .3H O, 361 [Sn(phen)(NO )] , HTB-26).
5
- Breast cancer cells, epithelial-like morphology
24. FAB-mass (m/z): 181 (phen).H , 217 (phen). MDA-MB-231 (American Type Culture Collection ATCC
+
+
+
+
2
2
3
+
41 [Sn(phen) (NO )] .
- Human epithelial colorectal carcinoma HT-29
American Type Culture Collection ATCC HTB-38).
- Epithelial cervix adenocarcinoma HeLa (American
2
3
(
2
0
0
.1.4. Synthesis of Sn(5-NH -phen)(OH)(Cl)(H O) (3)
2 2
.096g(0.450mmol)5-amino-1,10-phenanthroline•H O, Type Culture Collection ATCC CCL-2).
2
.148
g
(0.627 mmol) Ca(NO ) •4H O, 0.141
g
- Differentiated hepatocellular liver carcinoma
3
2
2
(
0.625 mmol) SnCl •2H O and 2.5 mL of 96% ethanol HepG2 (American Type Culture Collection, Rockville,
2 2
were dissolved in 20 mL distilled water at 70°С. The MD, USA).
1036

N. Kaloyanov et al.
-
-
Non-tumour diploid cell line Lep-3 (as a control).
of metal complexes described (1-4) are characteristic
C) observed in their
MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3- stretching vibrations (νC
-
-1
-1
carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- FTIR spectra. They range from 1513 cm to 1519 cm ,
tetrasolium inner salt].
-
1
while the corresponding value for o-phen is 1503 cm
-1
and for 5-NH -phen is 1505 cm . Also in the spectra
2
2
.3. Toxicity was determined by the MTS-test
of complexes 1, 3 and 4 absorption bands typical for
-1
All cells were raised in culture medium DMEM the organic ligand, in the range of 3324 - 3350 cm
-
1
supplemented with 10% fetal calf serum (FCS) and 100U for νas NH as well as of 3225 -3227 cm for ν NH ,
2
s
2
penicillin, incubated with ascending 10-fold dilutions of were clearly observed. In all spectra of the compounds,
-
1
the initial (4 mg mL ) substance solutions. Cells were the signals for H O molecule stretching vibrations
2
-1
seeded in 96-well flat-bottomed microplates (Orange (3404 - 3490 cm ) were also presented. In the case of
scientific) at a concentration of 2×10 cells/well. At the 1 and 3, signals for OH anions overlaped with those
4 h of incubation at 37 C under 5% carbon dioxide and for νas NH groups. Two other characteristic bands in
4
-
th
o
2
2
9
5% air atmosphere to each sample were added 20 µL FTIR spectra of compounds 1, 2 and 4 were those
-
-1
MTS. Each amount was applied in 4 wells. Samples of for NO3 anions in the ranges (1362 - 1385 cm ) and
-1
cells grown in non-modified medium served as a control. (822-824 cm ). Unfortunately, detailed structure studies
The absorbance of each well at 490 nm was read by of the new complexes by X-ray diffraction analysis were
an automatic microplate reader (Absorbance Reader not possible because of the difficulties in obtaining
“
Tecan” (Austria). Relative cell viability, expressed as suitable single crystals.
a percentage of the untreated control (100% viability),
The sensitivity of some human cell lines, expressed
was calculated for each quantity. Applied amount as % vitality, to different amounts of the tested
response curves were constructed manually for each substances are presented in Figs. 1-5.
experiment. All data points represent an average of
three independent assays.
The normal diploid cell line (Lep-3) (Fig. 1) showed
a proliferative response (vitality above 100%) when
incubated with lower substance amounts, with exception
of 2. It is worth noting that this complex showed slight
toxicity (80% vitality) even at high concentration.
Compound 4, containing a lead atom, was not toxic to
3. Statistical analysis
Statistical deviations were calculated automatically by normal cells at all concentrations tested.
Excel 2007 software program.
All tumour cell lines used were sensitive to the
four compounds in a different way, but the general
trend was that all these substances suppressed the
cells’ proliferation capacity. Most sensitive were HeLa,
followed by MDA-MB-231 and HepG2 cells (Figs. 2,4,5).
4
. Results and discussion
Compound 1, intheformof yellow crystals, wasobtained Human epithelial colorectal carcinoma HT-29 (Fig. 3)
through a static self-assembly process by interaction of line was affected by substances tested only in their high
5
-NH -phen and Sr(NO ) in water-alcohol media under doses. The most sensitive HeLa cells revealed almost
2
3
2
mild conditions. For this process to be energetically equal inhibition by the examined substances at low
-
2
favorable, reducing the Gibbs free energy is necessary. quantities, but above 4×10 mg their vitality was about
Thus the self-assembled structure is thermodynamically 20-25%. The complexes tested increased vitality of
-
2
more stable than the raw, unassembled components.
MDA-MB-231 (Fig. 2) at amounts below 4×10 mg and
Compounds 2 and 3 were produced as a result of in comparison to HeLa it reached level up to 70-75%.
2
+
competitive reactions between two metal cations (Sn
From Fig. 3, one can realize that human colorectal
2
+
andCa )withphenor5-NH -phen.Asmightbeexpected, cancer line was inhibited by all compounds only at 4
2
in both synthesis, complexes containing only one metal and 0.4 mg but proliferated quickly (above 100%) at
atom (Sn) were formed. Compound 4, containing lead, their lower concentrations. HepG2 did not reach 100%
was obtained in a similar way via interaction between vitality in all cases, but nevertheless it was not as
Pb(CH COO) •3H O, Ca(NO ) •4H O and 5-NH -phen sensitive as HeLa line (Figs. 4,5). Complex 3 was not
3
2
2
3
2
2
2
under mild conditions. This is possible because tin and so strongly toxic towards hepatocellular liver carcinoma
lead are p-elements and unlike alkaline earth metals like other compounds.
rapidly form complexes via covalent bonds with the
The lack of inhibition effect of all lower substance
ligands used. Additional evidence for the formation doses as well as of 4 and 2 (particularly at their high
1037

Synthesis and biological activity of novel heavy metal complexes
of 5-amino-1,10-phenanthroline and 1,10-phenanthroline
Figure 1. Vitality (%) of non-tumour human diploid cells Lep-3 (as a control), treated with substances 1- 4.
Figure 2. Vitality (%) of human breast cancer cells, epithelial-like morphology MDA-MB-231, treated with substances 1- 4.
quantities) toward normal diploid cells (Fig. 1) is a sign showed compounds 1 and 4 at their high amounts as
-
2
that these compounds can be used potentially as non- well as 1 at its lower ones (≤ 4×10 mg). Therefore,
toxic tumour inhibitors. the strontium complex of 5-amino-o-phenanthroline
Comparing the effects of 2 and 3 to normal cells, it displays the widest anticancer activity spectrum as well
was found that in high amounts 2 was less toxic. The as the least toxicity to non-tumour cells at low doses.
general trend is that 3 was a weaker tumour inhibitor This makes 1 suitable for further in-depth studies
against HepG2, but the activity of both compounds was in vivo. These results are in good agreement with
comparable to other lines. The priority of 3 at low doses our previous studies where the complex of 5-amino-
was a less pronounced toxicity to Lep-3, compared 1,10-phenanthroline with Pd(ІІ) again demonstrated
with 2, probably due to the presence of electron donor
amino group directly connected to the phenanthroline This complex displayed the longest mean survival
aromatic system at fifth place. time (2.2 times longer than the controls) in
a
well
pronounced
antitumour
activity.
Insummary,itcanbestatedthatthebestpronounced hamsters infected with cancerous (100% lethality)
inhibitor activity against the four human tumour lines myeloid subcutaneous tumour [12]. In addition,
1038

N. Kaloyanov et al.
Figure 3. Vitality (%) of human epithelial colorectal carcinoma HT-29, treated with substances 1- 4.
Figure 4. Vitality (%) of human epithelial cervix adenocarcinoma HeLa, treated with substances 1- 4.
Figure 5. Vitality (%) of human differentiated hepatocellular liver carcinoma HepG2, treated with substances 1- 4.
1039

Synthesis and biological activity of novel heavy metal complexes
of 5-amino-1,10-phenanthroline and 1,10-phenanthroline
Table 1. In vitro proliferative effects of 1 - 4 towards MDA-MB-231, HT-29, HeLa, HepG2 and Lep-3 cells.
Compound
EC50 ± SE (M)
MDA-MB-231
HT-29
HeLa
Hep G2
Lep-3
1
6.31 e-6 ± 0.404
4.23 e-5 ± 0.361
1.36 e-4 ± 0.390
6.44 e-5 ± 0.416
6.24 e-5 ± 0.545
1.14 e-3 ± 0.524
1.40 e-3 ± 0.658
7.68 e-4 ± 0.701
4.01 e-5 ± 0.234
6.50 e-4 ± 0.158
2.76 e-4 ± 0.219
2.67 e-4 ± 0.217
3.12 e-6 ± 0.594
7.61 e-5 ± 0.407
1.76 e-4 ± 0.387
6.00 e-3 ± 0.483
1.27 e-7 ± 0.457
2
ND
ND
ND
3
4
N.D. - not determined
Table 2. In vitro suppresion of Lep-3 cells.
5. Conclusions
Compound
IC50 ± SE (M)
A new metal complex Sr(5-NH -phen) (NO )(OH)(H O)
2
2
4
3
2
2
3
4
4.44e-1 ± 0.133
(1) was synthesized via a static self-assembly process.
6.88e-5 ± 0.465
7.52e-4 ± 0.328
Three novel coordination compounds: Sn(phen)(NO3)
(OH)(H O) (2), Sn(5-NH -phen)(OH)(Cl)(H O) (3) and
2
2
2
Pb(5-NH -phen)(NO ) (H O) (4) were obtained via
2
3
2
2
Pd(5-NH -phen) (NO )
3 2
showed good stimulation metal competitive reactions in a water-alcohol solution
2
2
of the antibody-producing B-cells and of all under mild conditions.
lymphocytes as well as did not show any histological
The cytotoxicity of complexes 1- 4 was measured
alterations and cytotoxic effect on White Wistar using some cultivated human tumour cell lines (MDA-
rats [13].
Having in mind the MTS proliferation assay is
MB-231, HT-29, HeLa and HepG2).
As it was expected all substances showed different
based on the fact that MTS tetrazolium compound is activities depending on the cell line and amount of the
bioreduced by cells into a colored formazan product, compound tested. The best pronounced cytotoxic effect
soluble in the tissue culture medium and this conversion on all cancer lines showed 1 and 4 at their high doses
-
2
is accomplished by NADPH or NADH, produced by as well as 1 at its lower ones (≤ 4×10 mg). Therefore,
dehydrogenase in metabolically active cells [19], we the strontium complex of 5-amino-o-phenanthroline
undertook the presented investigation. The bigger (1) exhibited the widest antitumour activity spectrum
release amount of formazan indicates to a higher vitality although having no toxicity towards non-tumour cells at
-
2
of the cells (proliferation). The low vitality demonstrates quantities ≤ 4×10 mg.
a cytotoxic influence of the experimental compounds.
Calculated EC50 values of 1-4 against all tumour cell
The calculated EC50 values of 1-4 against MDA-MB- lines used varied from 1.40×10 to 6.31×10 M.
-
3
-6
-
3
2
31, HT-29, HeLa and HepG2 varied from 1.40×10
-
6
to 6.31×10 M (Table 1). Substances 2-4 showed
IC50 against Lep-3 from 7.52×10 to 0.44 M (Table 2).
Compound 1 possess EC =1.26×10 M to the normal
-
4
-7
5
0
non-tumour human cells.
References
[
[
[
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