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ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 6, pp. 1256–1263. © Pleiades Publishing, Ltd.

, 2017.

Synthesis, Characterization, and Antitumor Activity


of New Copper(I) and Mercury(II) Complexes1
S. A. Aly*
Department of Environmental Biotechnology, Genetic Engineering and Biotechnology Research Institute,
Sadat City University, Egypt
*e-mail: Drsamali8@gmail.com

Received February 3, 2017

Abstract—A series of new copper(I) and mercury(II) complexes with 4-aminoantipyrine, semicarbazide, and
thiosemicarbazide ligands [(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)carbonohydrazonoyl
dicyanide (HL1), 2-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-[(E)-(3-methylphenyl)-
diazenyl]acetamide (H2L2), (Z)-2-cyano-N′-[(E)-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-
methylidene]-2-(2-phenylhydrazinylidene)acetohydrazide (HL3), 2-(anilinoacetyl)-N-phenylhydrazine-1-carbo-
thioamide (H2L4), 2-(anilinoacetyl)-N-(3-methylphenyl)hydrazine-1-carbothioamide (H2L5), and 2-anilino-N′-
[(E)-(2-hydroxyphenyl)methylidene]acetohydrazide (H2L6)] have been prepared and characterized by physical
and spectral data, including microanalysis, IR and UV-visible spectra, conductivity measurements, and thermal
analyses (DTG/TGA). The ligands H2L2 and HL3 produced dinuclear complexes. Thermal studies revealed that
the copper(I) complexes are thermally more stable than mercury(II) complexes. The copper complexes
exhibited potent inhibitory effect on the MCF7 human breast carcinoma cell line, as compared to mercury(II)
complexes.
Keywords: Anticancer activity, Cu(I) complexes, Hg(II) complexes, IR, UV, TGA
DOI: 10.1134/S1070363217060214

Synthetic compounds containing a five-membered selectivity for hormone-responsive cancers [15]. A


pyrazole ring [1] are exceptionally important in large number of bis-thiosemicarbazones and their copper
medicinal chemistry [2]. In particular, 4-aminoanti- complexes showed promising antitumor activity [16].
pyrine is important in inorganic and coordination
Metal complexes with hydrazones are known to
chemistry due to formation of stable complexes with
exhibit a broad spectrum of biological and pharma-
many transition metal ions. It is widely used in
ceutical activity, including inhibition of tumor growth
analytical and biological chemistry, and has thera-
[17–19], antioxidant, antimicrobial, and antiviral
peutic utility [3–4] as anti-inflammatory [5–6] and
activities [20–22]. Salicylaldehyde benzoylhydrazone
chemotherapeutic agent [7]. 4-Aminoantipyrine is an
appeared to be an unusually potent inhibitor of DNA
intermediate product in the synthesis of antipyretic and
synthesis and cell growth in a variety of human and
analgesic drugs [8]. Recent studies of copper(II),
rodent cell lines [23].
zinc(II), and mercury(II) complexes with 4-amino-
antipyrine and thiocyanate ligands [9] showed The goal of the present work was to prepare some
moderate antifungal activity of Cu(II) and Zn(II) copper(I) and mercury(II) complexes with the follow-
complexes as compared to the free ligands. ing ligands: (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-
1H-pyrazol-4-yl)carbonohydrazonoyl dicyanide (HL1),
Thiosemicarbazones play a significant role in many
2-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-
biological systems [10–12] and are known for their
1H-pyrazol-4-yl)-2-[(E)-(3-methylphenyl)diazenyl]-
ability to act as multidentate ligands toward transition
acetamide (H2L2), (Z)-2-cyano-N′-[(E)-(1,5-dimethyl-3-
metal ions through various combinations of donor
oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methyl-
nitrogen, sulfur, and oxygen atoms [13, 14]. Thiosemi-
idene]-2-(2-phenylhydrazinylidene)acetohydrazide (HL3),
carbazones have been intensively studied due to their
2-(anilinoacetyl)-N-phenylhydrazine-1-carbothioamide
inhibitory action on ribonucleotide reductase and
(H2L4), 2-(anilinoacetyl)-N-(3-methylphenyl)hydrazine-
1
The text was submitted by the author in English. 1-carbothioamide (H2L5), and 2-anilino-N′-[(E)-(2-

1256
SYNTHESIS, CHARACTERIZATION, AND ANTITUMOR ACTIVITY OF NEW COPPER(I) 1257

Scheme 1.
CN O
CN Me H CN
H N Me
N N H
NC N N Ph N
N Me Me N O N N N Me
N
N Me HN O N
O Me O
Ph Ph Ph
1 2
HL H2L H2L3

S OH
1H
H
Ph N 2 C3 4 Ph N
N N N R N N
H H H H
O O
4,
H2L H2L 5 H2L6

OH2
Cl CN Me
CN Me H
H Cu N
N CN H O N N
NC N N Me
X N Me N HN O
Ph N N AcO–
O M N N Ph Ph O
N O Me NH O H2O OH2 Ph
Y Ph N
Me N N CN Me Hg Hg
N Cu Me OH2
H2O O
Me H Cl OH2 OH
CN H
1, 2 3 4
S S
H H H Me H
H Ph N Ph
Ph N Ph Ph N N N N N
N N N N N H
H H H H O H H
O O S Hg
Cu M
OH2 AcO OAc
Cl OH
5 6 7
Ph N
N N
H
O
O
H2O M H
O O

Me
8
H2L4, R = H; H2L5, R = Me; 1, M = Cu, X = Cl, Y = H2O; 2, M = Hg, X = OAc, Y = OH.

hydroxyphenyl)methylidene]acetohydrazide (H2L6), and readily soluble in DMF and DMSO. The molar
characterize then by physical and spectral data, conductivities of 1–8 in DMF (c = 10–3 M; Table 1) show
including microanalysis, IR and UV-visible spectro- that the complexes (except for 4) are essentially non-
scopy, conductivity measurements, and thermal analyses electrolytes, indicating non-coordination of the anions;
(DTA/TG), and estimate their antitumor activity. complex 4 behaved as a 1 : 1 electrolyte [24].
The reactions of copper(I) chloride and mercury(II) The 1H NMR spectra of ligands HL1–H2L6 have
acetate with HL1–H2L6 at a 1 : 1 molar ratio produced been reported in [25–29]. Comparison of the IR spec-
complexes 1–8; complexes 3 and 4 are dinuclear tra of the free ligands and their Cu(I) and Hg(II)
(Scheme 1). The complexes are air stable, non-hygro- complexes showed that HL1 is a bidentate ligand coor-
scopic, partially soluble in common organic solvents, dinating through the carbonyl oxygen and azomethine

RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017


1258 ALY

Table 1. Analytical and physical data of ligands and metal complexes


Comp. no.

Found, % Calculated, %

Yield, %
Ʌma
Compounds Color Formula M
C H M Cl C H M Cl

HL1 70 Orange–yellow 56.1 4.4 – – C14H14N6O2 56.4 4.7 – – 298


1 Cu(HL1)2Cl(H2O) 65 Green 49.9 4.0 9.7 5.4 CuC28H27N12O3Cl 49.6 3.8 9.4 5.2 677 10
1
2 Hg(HL )2(OH)(OAc) 60 Brown 43.3 3.0 24.3 – HgC30H30N12O5 43.0 3.3 24.0 – 837 8
H2L2 70 Yellow 65.2 5.6 – – C21H21N6O2 65.0 5.4 – – 389 –
2
3 [Cu2(H2L )Cl2(H2O)2]·3H2O 65 Dark brown 37.0 4.1 19.1 10.3 Cu2C21H31N6O7Cl2 37.2 4.4 18.8 10.5 677 11
HL3 65 Orange 63.1 4.5 – – C21H19N7O2 62.8 4.7 – – 401 –
3
4 [Hg2(L )(OH)2(H2O)4]·OAc 60 Pale brown 28.3 3.0 41.2 – Hg2 C23H31N7O10 28.5 3.3 41.5 – 967 127
H2L4 65 Pale brown 60.1 5.6 – – C15H16N4OS 60.0 5.3 – – 300 –
4
5 Cu(H2L )Cl(H2O) 70 Green 43.5 4.5 14.9 8.4 CuC14H18N6O3Cl 43.2 4.3 15.2 8.5 417 22
H2L5 65 Pale brown 61.2 5.9 – – C16H18N4OS 61.1 6.0 – – 314 –
5
6 Cu(H2L )(OH) 60 Green 48.5 4.8 16.3 – CuC16H19N4O2S 48.7 5.1 16.1 – 395 4.4
7 Hg(H2L5)(OAc)2 65 Buff 38.3 4.3 31.4 – HgC20H24N4O5S 38.0 4.0 31.7 – 633 8.2
6
H 2L 70 Pale brown 67.1 5.5 – – C15H15N3O2 67.0 5.6 – – 269 –
8 Hg(HL6)(OAc)(H2O) 65 Buff 37.2 4.0 36.8 – Hg C17H19N3O5 37.4 3.7 36.7 – 546 10.0
a
Ʌm is molar conductivity, Ω–1 cm2 mol–1; DMF, c = 10–3 M.

nitrogen atoms. Ligands H2L2 and HL3 produced remain at the same frequencies as in the spectra of the
dinuclear complexes 3 and 4. Ligands H2L4 and H2L5 free ligands or are slightly shifted, except for complex
are neutral bidentate (complexes 5, 7) or tridentate (6) 3 which showed lower frequencies. Thus, neither N–H
which coordinate through the side-chain carbonyl nor C≡N groups of the ligand participate in coor-
oxygen atom and NH nitrogen atom in complexes 5 dination in complexes 1 and 2. The side-chain C=O
and 7, and the sulfur atom is additionally involved in stretching band of the ligand disappears upon com-
complex 6. Ligand H2L6 in complex 8 is coordinated in plexation to form dinuclear complex 4. Ligands H2L4
a monobasic tridentate fashion through the azomethine and H2L5 show bands at 3310–3380, 3305– 3271, 3235–
nitrogen atom and enolic and phenolic oxygen atoms. 3165 (NH), 1690–1675 (C=O), and 750–761 cm–1 (C=S),
The IR spectra of the ligands and complexes 1–8 and three additional bands are observed for H2L6 at
are presented in Table 2. Generally, the IR spectra of 3400 (OH), 1605 (C=N), and 1275 cm–1 (C–O). The
free ligands HL1–HL3 showed four bands at 3200– ν(N–H) and ν(C=O) bands of complexes 5–7 appeared
3430, 2205–2210, 1630–1635, and 1590–1610 cm–1, at lower frequencies compared to the free ligands,
which were assigned to N–H, C≡N, C=O, and C=N indicating coordination through the corres-ponding
stretching vibrations; ligands H2L2 and HL3 addition- groups [33]. The IR spectrum of complex 8 showed
nally displayed bands at 1650–1660 and 1550– low-frequency shifts of the ν(C=N), ν(OH), ν(C–O),
1575 cm–1 due to side-chain C=O and N=N bonds, and δ(O–H) bands, whereas the ν(C=O) band
respectively. Metal complexes 1–3 are characterized disappeared. This means that the coordinated ligand
by reduced stretching frequencies of the pyrazolone has the enol imine structure. In addition, some new
and side-chain carbonyl groups and C=N bond, which medium to weak bands were observed in the IR spectra
is consistent with coordination through the corres- of all complexes at 655–455 and 510–420 cm–1, which
ponding donor atoms [30–32]. The bands corres- were tentatively assigned to ν(M–O) and ν(M–N)
ponding to ν(C≡N) and ν(N–H) in complexes 1–3 [34, 35].

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SYNTHESIS, CHARACTERIZATION, AND ANTITUMOR ACTIVITY OF NEW COPPER(I) 1259

Table 2. IR spectra (ν, cm–1) of ligands and metal complexes


Comp.
H2O/OH N4–H N2–H N1–H C≡N C=Oa C=Ob C=N N=N C=S M–O M–N
no.
HL1 –
– – 3200 2205 1630 – 1587 – – – –
1 3420 – – 3205 2231 1590 – 1500 – – 511 460
2 3436 – – 3064 2165 1611 – 1493 – – 581 453
2
H2L – – 3384 3204 2210 1661 1680 – 1610 – – –
3 3438 – 3355 – 2207 1630 1666 – 1500 – 454 429
3
HL – – 3430 – 2210 1633 1650 1537 1491 – – –
4 3437 – – – 2360 1610 – 1589 1500 – 650 423
4
H2L – 3460 3340 3250 – – 1677 – – 750 – –
5 3435 – 3284 3149 – – 1600 – – 755 503 439
H2L5 – 3380 3271 3166 – – 1675 – – 761 – –
6 3442 – 3286 3156 – – 1600 – – 755 448 497
7 3404 3134 3100 – – 1620 – – 753 612 509
6
H2L 3400 3360 3190 – – – 1690 – – – – –
8 3390 3282 – – – – – 1620 – – 603 473
a
Pyrazole ring. b Side chain.

The acetate ligand can coordinate to a metal center temperature, thermal decomposition begins, and the
in monodentate, bidentate, or bridging manner. The complexes melt together with decomposition in two
νas(COO–) and νs(COO–) frequencies of free acetate ion distinct stages. Complex 1 showed two endothermic
are ~1560 and 1416 cm–1, respectively. In the case of DTA peaks at 235–300 and 487–556°C due to loss of
monodentate coordination, the νas(COO–) frequency is H2O + Cl + C7H4N2 (weight loss 25.3%; calculated:
higher than 1560 cm–1, while the νs(COO–) frequency 25.0%). Complex 5 showed one endothermic and two
is lower than 1416 cm–1. As a result, the difference exothermic DTA peaks at 251–277, 382–428, and 456–
between the COO– stretching frequencies for mono- 578°C with weight losses of 20.0, 8.7, and 11.4%,
dentate coordination is much larger than for the free respectively (calculated: 20.1, 8.5, and 10.1%,
acetate ion, as found for complexes 2, 4, and 7 which respectively). Two endothermic and one exothermic
showed νas(COO–) at 1553–1605 cm–1 and νs(COO–) at DTA peaks were observed for complex 6 at 236–269,
1330–1385 cm–1 [36–38]. Complex 8 displayed two 461–541, and 553–590; the corresponding weight
bands at 1605 and 1418 cm–1 due to νas(COO–) and losses were 27.9, 16.3, and 6.9% (calculated: 27.8,
νs(COO–), respectively, and was assigned bidentate 16.7, and 6.6%, respectively). Complex 3 began to lose
coordination of the acetate ion [39]. In addition, the IR weight in the temperature range 46–80°C (one
spectra of 1, 3–6, and 8 showed a broad peak at 3390– endothermic DTA peak at 45–90°C, which was
3435 cm–1, indicating the presence of water molecules, assigned to loss of crystallization water; two exo-
and complex 4 showed one more band at 3437 cm–1 thermic DTA peaks at 238–350 and 419–492°C were
assigned to the coordinated hydroxy group [24]. related to weight losses of 16.3 and 18.0%, respec-
tively (calculated: 16.1 and 17.6%). The decomposi-
The thermal behavior of the obtained complexes
tion of complexes 1, 3, 5, and 6 was not complete until
was investigated by thermogravimetric and differential
600°C; i.e., these complexes may be regarded as mode-
thermal analysis (Table 3). Figure shows the DTA and
rately thermally stable.
TG curves of complexes 1–3, 5, and 6 recorded under
nitrogen atmosphere. No weight loss was found for Likewise, mercury(II) chelates 2, 7, and 8 decom-
complexes 1, 5, and 6 up to 235, 223, and 194°C, posed in two distinct stages starting at 169, 136, and
respectively, indicating the absence of solvent/water 157°C (Table 3). Complex 2 showed a strong exo-
molecules, which was also evident from their ele- thermic DTA peak at 169–213°C with a weight loss of
mental analyses and IR spectra. Above that 73.7% (calculated: 73.95%). Complex 7 displayed three

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Table 3. Thermal analysis data of Cu(II) and Hg(II) complexes


Comp. Weight loss, %
Complex DTA, °C TG, °C Lost species
no. found calculated
1 Cu(HL1)2Cl(H2O) 239–300 235–407 25.3 25.0 (H2O +Cl +C7H4N2)
487–556 at 600 Thermal stabilization
2 Hg(HL1)2(OH)(OAc) 169–213 169–234 73.7 73.95 ( 2L+ OAc)
3 [Cu2(H2L2)Cl2(H2O)2]·3H2O 45–90 46–80 7.8 8.0 3H2O
238–350 224–324 16.3 16.1 (2H2O+2HCl)
419–492 433–505 18.0 17.6 (C6H5NH2+C2H2)
4 [Hg2(L3)(OH)2(H2O)4]·OAc 189–244 145–296 15.6 15.3 (4H2O + OAc +OH)
278–358 249–342 25.1 25.0 (0.5L+C2H2O)
514–594 550–593 8.1 8.0 C6H5
5 Cu(H2L4)Cl(H2O) 251–277 223–286 20.0 20.1 (H2O + C4H4N)
382–428 296–353 8.7 8.5 Cl
456–578 445–545 10.4 10.1 C2H2O
6 Cu(H2L5)(OH) 236–269 194–276 27.9 27.8 (OH+ C6H5NH2)
461–541 293–360 16.3 16.7 (C4H4N)
553–590 510–600 6.9 6.6 (C2H2)
7 Hg(H2L5)(OAc)2 163–195 136–207 9.0 9.3 OAc
224–262 226–326 24.3 24.0 (OAc + C6H5NH2)
444–485 452–553 21.6 21.2 (C7H4NS)
485 570
8 Hg(HL6)(OAc)(H2O) 228–257 157–211 6.4 6.2 (H2O +NH2)
431–481 216–347 69.0 68.94 Decomposition reaction

Table 4. Cytotoxicity of some ligands and complexes against MCF-7 cell line

Inhibition, %
Compound IC50, μM
1 µM 10 µM 100 µM
HL1 62.6±11.7 65.5±11.3 66.7±12.1 0.78
1
Cu(HL )2Cl(H2O) 88.8±15.6 93.6± 13.1 93.3±15.1 0.56
1
Hg(HL )2(OH)(OAc) 83.3±11.3 85.9±21.1 88.5±18.2 0.60
4
H2L 59.3±11.0 62.5±10.6 64.7±11.3 0.84
4
Cu(H2L )Cl(H2O) 85.0±14.6 88.5±14.0 88.2±14.1 0.59
5
H2L 58.8±11.0 62.0±10.4 63.5±11.0 0.85
5
Cu(H2L )(OH) 89.0±16.0 94.5±14.3 94.2±15.3 0.56
5
Hg(H2L )(OAc)2 80.0±11.2 82.0 ±19.7 83.7±17.3 0.63
6
H2L 64.0 ±11.8 65.6±11.5 67.6±11.7 0.78
6
Hg(HL )(OAc)(H2O) 81.3±11.3 83.5±15.3 85.7±15.0 0.62
Doxorubicin 75.5±12.4 80.4±17.0 87.3±18.3 0.66

weak exothermic and one weak endothermic DTA plex 8 with weight losses of 6.4 and 68.9%, respec-
peaks at 163–195, 224–262, 444–485, and 485–570°C tively (calculated: 6.2 and 68.9%). Complex 4 showed
(weight loss 9.0, 24.3, and 21.5%; calculated: 9.3, three exothermic DTA peaks at 189–244, 278–358,
24.0, and 21.2%, respectively). Two exothermic DTA and 514–594°C (weight loss: 15.6, 25.1, and 8.1%;
peaks appeared at 228–257 and 431–481°C for com- calculated: 15.3, 25.0, and 8.0%).

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SYNTHESIS, CHARACTERIZATION, AND ANTITUMOR ACTIVITY OF NEW COPPER(I) 1261

(a) Sample weight 4.5 mg (b) Sample weight 3.1 mg

2
TGA, mg

TGA, mg
1

1
2

Temperature, °C Temperature, °C
(c) Sample weight 3.2 mg (d) Sample weight 3.2 mg

1
TGA, mg

TGA, mg

2
1

Temperature, °C Temperature, °C

(e) Sample weight 4.8 mg


TGA, mg

Temperature, °C
(1) TG and (2) DTA curves of copper(I) complexes (a–d) 1–3, 5, and (e) 6.

Table 4 contains the results of studying the and H2L4), their copper(I) and mercury(II) complexes
cytotoxic activity of some ligands and complexes in demonstrated significant inhibitory action against
vitro, which was expressed as percentage of inhibition MCF7 cell line in dose-dependent manner. Copper(I)
of MCF7 proliferation. In contrast to the ligands (HL1 complexes 1 and 6 exhibited a significant increase in

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1262 ALY

the cytotoxicity against MCF7 as compared to doxo- a solution of the corresponding ligand (HL1, H2L2,
rubicin taken as reference anticancer drug. H2L4, or H2L5 for copper complexes or HL1, HL3,
H2L5, or H2L6 for mercury complexes) in anhydrous
In summary, we have synthesized and structurally
ethanol. The mixture was magnetically stirred at 60°C
characterized new copper(I) and mercury(II) com-
for 2–5 h. The resulting solid was filtered off, washed
plexes with 4-aminoantipyrine, thiosemicarbazide, and
several times with ethanol, and dried over P4O10 in a
hydrazide ligands. The thermal study revealed that the
vacuum.
copper(I) complexes are more thermally stable than
mercury(II) chelates. The copper complexes showed
Antitumor activity. Potential cytotoxicities of
higher cytotoxicity against human breast carcinoma
ligands HL1, H2L4, H2L5, and H2L6 and complexes 1, 2,
MCF7 cell line as compared to mercury complexes and
and 5–8 against human breast adenocarcinoma cell line
are therefore promising as anticancer drugs.
MCF7 (ATCC, cat. no. HTB-22) were evaluated at the
EXPERIMENTAL National Cancer Institute (Cairo University, Egypt) by
the colorimetric sulforhodamine B (SRB) assay accord-
All organic reagents and solvents were purchased ing to [40, 41]. The cells were grown in Dulbecco’s
from Fluka or Merck (Nasr City, Egypt) and were used Modified Eagle’s Medium with 4.5% of glucose
without further purification. The elemental analyses (DMEM, PAA Laboratories) supplemented with 10%
(C, H, Cl) were obtained as the Microanalytical Unit of fetal calf serum (FCS). Cells were seeded into 96-well
the Cairo University, Egypt. The Fourier Transform microliter plates at a density of 5000 cells per 0.1 mL
Infrared (FT-IR) spectra (4000–400 cm–1) were per well and 24 h after seeding were exposed in
recorded in KBr on a Thermo Nicolet Nexus 670 FTIR triplicate to three dilutions (1, 10, 100 μM) of samples
spectrometer (Central Lab, El Minufiya University, dissolved in dimethyl sulfoxide (DMSO). Control and
Egypt). The 1H NMR spectra were recorded in DMSO-d6 blank wells were included in each plate. After 72 h,
using a Varian NMR spectrometer (300 MHz; Micro- cells were fixed in trichloroacetic acid (TCA) (25 μL
analytical Lab, Cairo University, Egypt). The molar of 50% w/v TCA per well) for 1 h at 4°C, washed five
conductivity measurements were made in DMF (10–3 M) times with distilled water, and stained with 50 μL of
using a Tacussel Conductometer type CD6N. 0.4% SRB in 1% acetic acid for 30 min. The cells were
washed five times with 1% acetic acid and air-dried.
Thermal analyses (DTA/TG) were obtained using a The stain was solubilized in 10 mM TRIS (pH 10.5),
Shimadzu DTA/TG-50 Thermal analyzer (Central Lab, and light absorption was measured using a microplate
El Minufiya University, Egypt) at a heating rate of reader (Thermo Lab Systems) at λ 492 nm with
10 deg/min in a nitrogen atmosphere (nitrogen flow reference wavelength λ 690 nm. The cytotoxicity was
rate 20 mL/min) in the temperature range from 25 to expressed as a percentage of the corresponding control
800°C using platinum crucibles. value (non-treated cells) obtained in two independent
The ligands, (1,5-dimethyl-3-oxo-2-phenyl-2,3-di- experiments. The original data was analyzed by a one
hydro-1H-pyrazol-4-yl)carbonohydrazonoyl dicyanide way ANOVA, followed by Duncan’s multiple-range
(HL1), 2-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3- post-hoc test. Differences were considered significant
dihydro-1H-pyrazol-4-yl)-2-[(E)-(3-ethylphenyl)di- at P <0.05.
azenyl]acetamide (H2L2), (2Z)-2-cyano-N′-[(E)-(1,5-
dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4- REFERENCES
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3rd ed. p. 354.
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New Age International Publisher, 2010, 4th ed., p. 454.
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SYNTHESIS, CHARACTERIZATION, AND ANTITUMOR ACTIVITY OF NEW COPPER(I) 1263

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