Synthesis, spectroscopic characterization and in vitro anticancer activity of new platinum(II) complexes with some thione ligands?in the presence of triethylphosphine

Article abstract of DOI:10.1007/s10534-017-0047-5

Seven new platinum(II) complexes (1–7) of triethylphosphine (Et₃P) and thiones (L) with general formula, cis-[Pt(Et₃P)₂(L)₂]Cl₂ were prepared and characterized by elemental analysis, FTIR and NMR (¹H, ¹³C & ³¹P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1–6 are much better than cisplatin and carboplatin as indicated by their IC₅₀ values.

Full text of DOI:10.1007/s10534-017-0047-5

Biometals
DOI 10.1007/s10534-017-0047-5
Synthesis, spectroscopic characterization and in vitro
anticancer activity of new platinum(II) complexes with
some thione ligands in the presence of triethylphosphine
.
Mohammed Yagoub Jomaa Muhammed Altaf Saeed Ahmad
.
.
.
Gaurav Bhatia Jatinder Singh Saleh Altuwaijri Anvarhusein A. Isab
.
.
Received: 17 May 2017 / Accepted: 21 August 2017
Ó Springer Science+Business Media, LLC 2017
Abstract Seven new platinum(II) complexes (1–7)
of triethylphosphine (Et P) and thiones (L) with
activity values of compounds 1–6 are much better than
cisplatin and carboplatin as indicated by their IC50
values.
3
general formula, cis-[Pt(Et P) (L) ]Cl were prepared
3
2
2
2
and characterized by elemental analysis, FTIR and
1
13
31
NMR ( H, C & P) measurements. The analytical
and spectroscopic data suggested the formation of the
desired complexes. The complexes were tested for
in vitro cytotoxicity against four cell lines: Hela
Keywords Anti-cancer activity Á Pt(II) complexes Á
Thione ligands Á Cancer cell lines
(
human cervical adenocarcinoma), MCF-7 (human
breast carcinoma), A549 (human lung carcinoma), and
HTC15 (human colon carcinoma). The anticancer
Introduction
Platinum complexes are very important from the
medicinal point of view because of the successful use
M. Y. Jomaa Á A. A. Isab (&)
of cisplatin, cis-[Pt(NH ) Cl ] and its derivatives for
3 2 2
Department of Chemistry, King Fahd University of
Petroleum and Minerals, Dhahran 31261, Saudi Arabia
e-mail: aisab@kfupm.edu.sa
the treatment of a number of cancers (Johnstone et al.
016; Wheate et al. 2010; Wilson and lippard. 2014;
Dilruba and Kalayda. 2016; Dasari and Tchounwou
014; Komeda 2011; Kelland 2007; Zutphen and
2
M. Altaf
2
Center of Research Excellence in Nanotechnology, King
Fahd University of Petroleum & Minerals,
Dhahran 31261, Saudi Arabia
Reedijk 2005; Hambley 2001; Ahmad et al. 2006).
The antitumor activity of cisplatin is believed to
depend on its ability to modify the structure of the
DNA of cancer cells in such a way that its enzymatic
excision repair is avoided (Ahmad 2010; Jamieson and
Lippard 1999; Jung and Lippard 2007; Wong and
Lippard 2005). The main biochemical mechanism of
cisplatin action involves cellular uptake and hydrati-
zation of the complex, monofunctional adduct forma-
tion, closure to a bifunctional adduct, distortion of the
DNA helix, and recognition of this distortion by
cellular proteins (Zutphen and Reedijk 2005; Hambley
2001 and Ahmad et al. 2006; Ahmad 2010; Jamieson
S. Ahmad
Department of Chemistry, College of Sciences and
Humanities, Prince Sattam bin Abdulaziz University,
Al-Kharj 11942, Saudi Arabia
G. Bhatia Á J. Singh
Department of Molecular, Biology & Biochemistry, Guru
Nanak Dev University, Amritsar 143005, India
S. Altuwaijri
Clinical Research Laboratory, SAAD Research
Development Center, SAAD Specialist Hospital,
Al-Khobar 31952, Saudi Arabia
123

Biometals
and Lippard 1999). The downstream effects activate
the replication inhibition processes that ultimately
lead to cell death (Ahmad 2010; Jamieson and Lippard
Experimental
Materials
1
2
999; Jung and Lippard 2007; Wong and Lippard
005).
Cis-bis(triethylphosphine)dichloridoplatinum(II),
[(Et P) PtCl ] was purchased from Strem Chemicals,
Inc. Carbon disulfide (CS ) and diamines i.e., 1,2-
diaminoethane, N-methyl-1,2-diaminoethane, N,N’-
dimethyl-1,2-diaminoethane, N,N’-diethyl-1,2-di-
Although DNA is considered as the major target of
3
2
2
platinum complexes, the soft platinum(II) ion also
possesses strong affinity towards sulfur-containing
ligands such as methionine and glutathione (Messori
and Merlino 2016; Timerbaev et al. 2006; Wang and
Guo 2007; Sooriyaarchchi et al. 2016; Reedjik 1999).
It has been found that cisplatin-like drugs can induce
renal toxicity in chemotherapy due to their reactions
with the cysteine and methionine groups of proteins
2
aminoethane, 1,3-diaminopropane, N-ethyl-1,3-di-
aminopropane, 1,4-diaminobutane, were obtained
from Sigma-Aldrich Chemical Co. Germany. Dul-
becco’s Modified Eagle Medium (DMEM), (3-(4,5-
Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bro-
mide) (MTT), Dimethylsulfoxide (DMSO) and
deuterated solvents were also obtained from Sigma-
Aldrich
(
Reedjik 1999; Hartmann and Lipp 2003; Screnci and
Mckeage 1999). Several platinum(II) complexes with
thiones have been found to possess anticancer prop-
erties (Marverti et al. 2008; Fuks et al. 2010; Mustafa
et al. 2014; Mustafa et al. 2015; Augustus et al. 2003).
Platinum(II) complexes with thiourea ligands demon-
strated a different binding mechanism to DNA than
that of cisplatin. Sulfur donors are known to replace
chlorido ligands without prior solvolysis of the Pt–Cl
bond (Martins et al. 2001). The platinum(II) complex,
The thione ligands were synthesized following a
literature procedure by the reaction of carbon disulfide
(CS ) with diamines in diethyl ether solvent. The
2
adduct was then heated at 100–110 °C for 2–3 h. The
yellow product was recrystallized from methanol
(Ahmad et al. 2002).
[
Pt(en)Cl(1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylth-
2
Instrumentation
?
iourea)]
does not induce bifunctional covalent
adducts (cross-links) in DNA but acts through a
mechanism that involves monofunctional platination
and intercalation of the planar chromophore into the
DNA base stack. This type of adduct, which causes
local unwinding of double-stranded DNA by 21°, is
considered a potential cytotoxic lesion of the drug
Elemental analyses were performed on Perkin Elmer
Series 11 (CHNS/O) Analyzer 2400. The solid state
FTIR spectra of the ligands and their platinum(II)
complexes were recorded on NICOLET 6700 FTIR
-
1
spectrophotometer over the range 4000–400 cm
NMR measurements were carried out on Jeol JNM-LA
.
1
500 NMR spectrophotometer at 297 K. The H,
13
(
Augustus et al. 2003).
C
3
and P NMR spectra were recorded at frequencies of
1
The potential anticancer activity of platinum(II)
1
3
complexes of thioureas encouraged us to synthesize
new platinum(II) complexes with thiourea derivatives
and to characterize them using different analytical
techniques. Recently, we have reported the synthesis,
crystal structure and cytotoxic activity of some
platinum(II) complexes of thiones (Mustafa et al.
500.01, 125.65 and 200.0 MHz respectively. The
C
1
NMR spectra were obtained with H broadband
decoupling and referenced relative to TMS. The
spectral conditions were: 32 k data points, 0.967 s
acquisition time, 1.00 s pulse delay and 45° pulse
angle.
2
014; Mustafa et al. 2015). In this study, we have
extended our investigation towards the synthesis of
mixed ligand platinum(II) complexes (1–7) of tri-
ethylphosphine and heterocyclic thiones. The com-
plexes were characterized by various spectroscopic
techniques and were also evaluated for in vitro
anticancer activity. The structures of thione ligands
used in this study are shown in scheme 1.
Synthesis of complexes
All the complexes were synthesized according to the
Scheme 2 as given below. Two equivalents of thiones
dissolved in 10 ml methanol were added drop wise to
0.25 g (0.5 mmol) [(Et P) PtCl ] dissolved in 10 ml
3
2
2
dichloromethane. Stirring the mixture for 3 h resulted
1
23

Biometals
Scheme 1 The structures
of thione ligands used and
their resonance assignment
5
6
5
4
5
4
6
4
7
N3
1N
R/
N3
1
N
N3
1N
2
2
2
S
R
H
R
H
H
S
S
(
1-4)
(5-6)
(7)
/
1
2
3
4
5
6
7
. R = R = H; Imidazolidine-2-thione (Imt)
/
. R = CH
3
, R = H; N-methylimidazolidine-2-thione (MeImt)
/
/
. R = R = CH
3
; N,N -dimethylimidazolidine-2-thione (Me2Imt)
/
/
. R = R = C
2
H
5
; N,N -diethylimidazolidine-2-thione (Et2Imt)
. R = H; 1,3-Diazinane-2-thione (Diaz)
. R = C ; N-ethyl-1, 3-Diazinane-2-thione (EtDiaz)
. 1, 3-Diazipane-2-thione (Diap)
2
H
5
Scheme 2 Synthesis of
Platinum Complexes 1–7
CH OH
3
[(Et P) PtCl ]
[(Et P) PtL ].2Cl
3 2 2
3
2
2
+ 2L
CH Cl
2
2
L = Imt, complex 1; MeImt, complex 2; Me
2
Imt, complex 3; Et Imt, complex 4; Diaz,
2
complex 5; EtDiaz, complex 6; Diap, complex 7.
-
Table 1 IR absorption bands for free ligands (cm ) and their
platinum(II) complexes
1
in a colored solution. The solution was filtered and
kept at room temperature. Solid powder was obtained
by slow evaporation of the solvent for all complexes.
Purity of the products was assessed through elemental
percentages of C, H, N, and S.
Species
m (C=S)
m (N–H)
m (Pt–P)
m (Pt–S)
Imt
510, 1199
496, 1034
520, 1200
514, 1052
516, 1201
511, 1048
514, 1199
408, 1088
510, 1206
509, 1038
505, 1217
499, 1043
527, 1190
522, 1034
3200
3531
3200
3418
–
–
–
1
272
–
305
–
[
Yield: 89%. C, H, N, and S% [Calculated C: 30.60,
(Et P) Pt(Imt) ]Cl (1). M. p. 223–225 °C,
3
2
2
2
MeImt
2
280
–
299
–
H: 5.99, N: 7.93, S: 9.08, Found: C: 30.49, H: 6.22, N:
1
.03, S: 8.91]. IR bands, H & C NMR chemical
13
8
Me
3
2
Imt
3
shifts, and P solution NMR (see Tables 1, 2, 3).
1
–
281
–
307
–
[
Yield: 82%. C, H, N, and S% [Calculated C: 32.70, H:
(Et P) Pt(MeImt) ]Cl (2). M. p. 246–250 °C,
Et
4
2
Imt
–
3
2
2
2
–
279
–
311
–
6
7
.31, N: 7.63, S: 8.73, Found: C: 32.49, H: 6.28, N:
Diaz
3210
3448
3210
3422
3214
3522
1
.82, S: 8.69]. IR bands, H & C NMR chemical
13
5
274
–
311
–
3
1
shifts, and P solution NMR (see Tables 1, 2, 3).
EtDiaz
[
Yield: 69%. C, H, N, and S% [Calculated C: 34.64, H:
(Et P) Pt(Me Imt) ]Cl (3). M. p. 214–216 °C,
6
282
–
309
–
3
2
2
2
2
Diap
7
6
7
.61, N: 7.35, S: 8.41, Found: C: 34.59, H: 6.68, N:
267
306
1
.42, S: 8.46]. IR analysis, H & C NMR chemical
13
3
1
shifts, and P solution NMR (see Tables 1, 2, 3).
123

Biometals
1
13
Table 2 H and C NMR
chemical shifts of the free
ligands and their complexes
Species
(Et P)
N–H C-2
C-4
–
C-5
–
C-6
N–C1 N–C2 P–C1 P–C2
[
3
2
PtCl
2
]
–
–
–
–
–
–
–
–
–
–
–
–
–
16.63 8.42
in CDCl
3
Imt
1
7.98
9.19
7.93
8.65
–
182.11 45.38 45.38
174.50 46.60 46.60
181.38 42.00 51.82
174.32 42.56 52.13
180.46 48.73 48.73
174.33 49.71 49.71
178.74 46.13 46.13
171.94 47.38 47.38
–
–
–
–
–
–
14.93 9.30
MeImt
2
34.35
34.47
34.80
35.16
42.69
43.77
–
–
–
–
–
13.82 8.11
Me
3
2
Imt
–
–
–
–
–
14.21 7.99
Et Imt
2
–
11.92
12.08
–
–
–
4
–
14.32 8.01
Diaz
7.77
9.13
7.70
8.32
7.70
8.50
173.34 38.36 19.29 38.36
166.68 41.53 19.92 41.53
–
–
5
–
–
14.37 8.82
EtDiaz
173.36 41.14 20.93 46.14 49.54
168.24 41.35 20.91 47.03 49.66
12.33
12.43
–
–
–
6
13.75 8.35
Diap
7
183.99 45.86 26.70 45.86
175.22 46.44 26.46 46.44
–
–
–
–
–
13.49 7.87
[
(Et P) Pt(EtDiaz) ]Cl (6). M. p.188–190 °C,
3
2
2
2
3
1
Table 3 P NMR chemical shift of the precursor and syn-
thesized complexes in CDCl
Yield: 67%. C, H, N, and S% [Calculated C: 36.45,
3
H: 6.88, N: 7.09, S: 8.11, Found: C: 36.21, H: 6.83, N:
1
195
J ( Pt– P), Hz
31
1
.23, S: 8.26]. IR bands, H & C NMR chemical
13
Species
(Et P)
d ppm
7
3
shifts, and P solution NMR (see Tables 1, 2, 3).
1
[
3
2
PtCl
2
]
7.2
9.2
8.6
9.1
9.0
9.2
8.3
7.8
2932
2244
2559
2358
2658
2273
2547
2300
[
(Et P) Pt(Diap) ]Cl (7). M. p.159–161 °C,
3
2
2
2
1
2
3
4
5
6
7
Yield: 77%. C, H, N, and S [calculated C: 34.64, H:
6
7
.61, N: 7.35, S: 8.41, Found: C: 34.33, H: 6.64, N:
1
.43, S: 8.37]. IR bands, H & C NMR chemical
13
3
1
shifts, and P solution NMR (see Tables 1, 2, 3).
In vitro cytotoxic activity
The shifts were measured relative to external reference,
phosphoric acid (0 ppm); each peak appeared as a triplet
with two satellites
In vitro cytotoxic activities of the synthesized com-
plexes, [(Et P) PtCl ], cisplatin and carboplatin were
3
2
2
evaluated against four human cancer cells; Hela
cervical cancer), A549 (lung cancer), MCF-7 (breast
(
cancer) and HTC15 (colon cancer) cell lines. The cells
3
[
Yield: 73%. C, H, N, and S% [Calculated C: 36.45, H:
(Et P) Pt(Et Imt) ]Cl (4). M. p. 189–191 °C,
were seeded at 4 9 10 cells/well in 100 lL DMEM
3
2
2
2
2
(Dulbecco’s Modified Eagle’s Medium) containing
10% FBS (Fetal Bovine Serum) in 96-wells tissue
culture plate and incubated for 72 h at 37 °C, 5% CO2
in the air and 90% relative humidity in the CO2
incubator. After incubation, 100 lL of the test sample;
complexes 1–7, [(Et P) PtCl ], cisplatin and carbo-
6
7
.88, N: 7.09, S: 8.11, Found: C: 34.51, H: 7.28 N:
1
.46, S: 8.56]. IR bands, H & C NMR chemical
13
3
1
shifts, and P solution NMR (see Tables 1, 2, 3).
[
Yield: 84%. C, H, N, and S% [Calculated C: 32.70,
(Et P) Pt(Daiz) ]Cl (5). M. p. 208–210 °C,
3
2
2
2
3
2
2
H: 6.31, N: 7.63, S: 8.73, Found: C: 32.41, H: 6.22, N:
platin (50, 25, 12.5 and 6.25 lM prepared in DMEM),
was added to cells and the cultures were incubated for
24 h. The medium of wells was discarded and 100 lL
1
.53, S: 8.66]. IR bands, H & C NMR chemical
13
7
3
1
shifts, and P solution NMR (see Tables 1, 2, 3).
1
23

Biometals
-
1
DMEM containing MTT (3-(4,5-Dimethylthiazol-2-
Yl)-2,5-Diphenyltetrazolium Bromide) (5 mg/mL)
was added to the wells and incubated in a CO2
incubator at 37 °C in dark for 4 h. After incubation, a
purple colored formazan (artificial chromogenic dye,
a product of the reduction of water insoluble tetra-
zolium salts e.g., MMT by dehydrogenases and
reductases) in the cells was produced and appeared
as dark crystals at the bottom of the wells. The medium
of culture was discarded from each well carefully to
avoid disruption of monolayer and 100 lL of
dimethylsulfoxide (DMSO) was added to each well.
The solution was thoroughly mixed in the wells to
dissolve the formazan crystals, which ultimately
resulted in a purple solution. The absorbance of the
near 3200 cm for m(N–H). Upon coordination, to
metals, the m(C=S) band shifts towards lower fre-
quency upon complexation, while the m(N–H) band
shifts to higher wavenumbers due to increasing in the
double bond character of the C–N bond (Ahmad et al.
2002; Isab et al. 2002; and Kennedy and Lever 1972).
A similar trend was observed in the present series of
the complexes and this implies that these ligands exist
in the thione form in the solid state.
The far-infrared spectra in the frequency region
-
below 400 cm have been recorded to investigate
1
m(M–S) and m(M–P) stretching frequencies, which lie
-
1
in the range of about 300 cm for the transition-metal
complexes according to the literature (Adam and
Cornell 1967). In all complexes, sharp peaks around
-
1
9
6-wells plate was taken at 570 nm with Labsystems
Multiskan EX-Enzyme-linked immunosorbent assay
EX-ELISA) reader against a reagent blank. The IC50
280 and 300 cm
were observed, which were
assigned to Pt–P and Pt–S stretching bands
respectively.
(
values were calculated from three independent exper-
iments by generating an equation of logarithmic trend
line of percentage cell viability against the concentra-
tion of compounds in Microsoft excel.
NMR Studies
1
13
All the signals detected in the H and C NMR spectra
of the appropriate thione ligand molecules were also
observed in the spectra of the synthesized Pt(II)
complexes. The N–H signal of thiones shifted slightly
toward high frequency from 0.8 to 1.4 with respect to
their positions in uncomplexed forms. These signals
were shifted as a consequence of the coordination of
ligands to the Pt(II) atom and the formation of the
targeting products. The deshielding of the N–H proton
is related to an increase of the p electron density in the
C–N bond upon complexation (Ahmad et al. 2002;
Results and discussion
IR spectroscopy
The selected IR vibrational bands for the free ligands
and their platinum(II) complexes are listed in Table 1.
In the IR spectra of thiones, the characteristic bands
were observed in three frequency regions; around 600
-
1
13
and 1100 cm for thiocarbonyl stretch, m(C=S), and
Isab et al. 2002). The C NMR chemical shifts of the
Table 4 IC50 values (in
lM) of the prepared
a
Compounds
IC50 ± SEM
compounds (1–7), the
precursor, cisplatin and
carboplatin against four
human tumor cell lines
HeLa
A549
MCF7
HCT15
Cisplatin
19.20 ± 1.81
56.47 ± 2.23
45.80 ± 2.33
1.40 ± 0.29
1.83 ± 0.26
1.50 ± 0.21
9.90 ± 1.65
2.23 ± 0.52
1.83 ± 0.35
17.27 ± 1.34
41.67 ± 1.17
71.20 ± 2.84
55.60 ± 2.53
3.50 ± 0.74
3.93 ± 0.47
2.37 ± 0.29
12.63 ± 1.09
4.50 ± 0.78
3.60 ± 0.72
27.73 ± 1.48
22.40 ± 1.37
55.63 ± 2.53
59.77 ± 2.15
4.67 ± 1.05
2.63 ± 0.88
3.77 ± 0.61
13.50 ± 1.36
4.73 ± 0.95
1.23 ± 0.34
22.33 ± 1.35
29.67 ± 2.35
63.90 ± 2.25
39.13 ± 1.98
7.03 ± 1.04
8.60 ± 0.93
4.23 ± 0.73
16.07 ± 1.13
6.87 ± 1.07
5.70 ± 0.91
37.10 ± 1.86
Carboplatin
[
3 2 2
Pt(Et P) Cl ]
1
2
3
4
5
6
7
a
Standard error of the mean
SEM) as standard
(
deviations determined from
at least three independent
experiments
123

Biometals
Fig. 1 Graph showing the
concentration dependent
in vitro cytotoxic effect of
complexes (1–7), precursor,
cisplatin and carboplatin on
the viability of HeLa cancer
cells
free ligands and their platinum(II) complexes are
This shift is likely due to back donation from platinum
d-orbital to the empty p* orbital of the thiocarbonyl,
which is known as strong p-accepting ligand, leading
the lone pair of phosphorus to shift electron density
towards platinum (Power and Wasylishen 1992;
Pidcock et al. 1966). As tabulated in Table 3, the
1
3
given in Table 2. In C NMR of all complexes, the
C = S resonance appeared upfield by 6–9 ppm com-
pared to free ligands. This shift is attributed to
decrease in the bond order of C=S bond upon
coordination. The increase in the double bond char-
acter of the C–N bond leads to a small downfield shift
in the C-N resonances (Ahmad et al. 2002; Isab et al.
1
31 195
coupling constant values J ( P, Pt) of the synthe-
sized complexes were decreased compared to the
precursor. This can be attributed to the strong trans
influence of the thiocarbonyl group of the thione
ligands compared to the chloride atoms in the case of
the precursor.
2
002).
In the P NMR of the complexes, three resonances
3
1
were observed with relative integral values of 1:4:1
around 8 or 9 ppm, as shown in Table 3. The NMR
1
95
active Pt nucleus (I = ‘) has a natural abundance
of 33.8%. Therefore, in P NMR two satellite peaks
3
1
In vitro cytotoxic effects of complexes 1–7
with the ratio of 1:1 were observed due to the presence
3
of heteronuclear coupling between P and Pt with a
1
195
The anticancer activity of complexes 1–7 as well as
[Pt(Et P) Cl ], cisplatin and carboplatin was exam-
1
195
31
high spin coupling constant ( J Pt– P). This high
spin coupling constant is in agreement with the values
reported in the literature for the bisphosphine in the
classic example of square-planar platinum(II) com-
plexes between 1462 and 5698 Hz (Pidcock et al.
3
2
2
ined against a panel of representative human tumor
cell lines, which include, human cervical adenocar-
cinoma (Hela), lung cancer cells (A549), breast
cancer cells (MCF7) and colon cancer cells (HCT15).
The results of in vitro cytotoxic activity are expressed
as IC50 and are presented in Table 4. The percentage
of cell viability at various concentrations of the
studied compounds is shown in Figs. 1, 2, 3 and 4.
The results displayed in Table 4 demonstrate that
six (1–6) of the seven prepared complexes exhibited
1
966; Mendia et al. 2006). The presence of a pair of
satellites points to the mononuclear structures of the
complexes similar to the reported ones (Mendia et al.
2
006).
The slight down field shifts were observed in all the
synthesized complexes as compared to the precursor.
1
23

Biometals
Fig. 2 Effect of
concentration of complexes
(
1–7), precursor, cisplatin
and carboplatin on the
viability of A549 cancer
cells
Fig. 3 Effect of
concentration of complexes
1
–7, precursor, cisplatin and
carboplatin on the viability
of MCF7 cancer cells
significantly higher activity than the standard anti-
cancer drugs (cisplatin and carboplatin) available in
the market, against all four cells. The precursor
complex, [Pt(Et P) Cl ] showed poor activity. The
in vitro cytotoxicity of complexes 1–3, 5 and 6 against
Hela (human cervical cancer) cell line is exceptionally
better than cisplatin (8–14 times) and carboplatin
(25–40) times. The antiproliferative activity of
3
2
2
123

Biometals
Fig. 4 Effect of
concentration of complexes
1
–7, precursor, cisplatin and
carboplatin on the viability
of HTC15 cancer cells
complex
IC50 = 1.23 ± 0.34 lM) is particularly remarkable.
It is about 20 times more effective than cisplatin and
5 times as compared to carboplatin. With respect to
6
against
the
MCF-7
cells
(1–6) were found to be more efficient than cisplatin
and carboplatin against Hela, A549, MCF-7 and
HTC15 cell lines. The significant in vitro cytotoxicity
of the synthesized complexes makes them strong
candidates for clinical testing as potential anticancer
agents for future drug discovery.
(
4
A549 and HCT15 cells, the complex 3 showed the
highest activity. Overall among the seven complexes
investigated, 3 was found to be the most effective,
while 7 was the least active against all cancer cell
lines. Ongoing from a non-ionic precursor, [Pt(Et3-
P) Cl ] to the ionic compounds (1–7) brought about a
Acknowledgement This research was supported by the King
Fahd University Petroleum and Minerals Research Committee
under project No. IN161005.
2
2
1
.05–50 times increase in the antiproliferative activity.
The strong in vitro anticancer effect of the Et P-
3
platinum(II)-thione complexes observed in the present
study could be related to the presence of a lipophilic
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