A novel Trans-Pt(II) complex bearing 2-acetoxymethylbenzimidazole as a non-leaving ligand (trans-[Pt(AMBi)2Cl2]): Synthesis, antiproliferative activity, DNA interaction and molecular docking studies compared with its cis isomer (cis-[Pt(AMBi)2Cl2])

Article abstract of DOI:10.1016/j.molstruc.2019.02.066

Trans-[Pt(AMBi)₂Cl₂ (1) in which AMBi is 2-acetoxymethylbenzimidazole, was synthesized and characterized by spectroscopic methods. Novel complex 1 was evaluated for its potential antiproliferative effect against three human cancer cell lines, including HeLa (human cervix cancer), MCF-7 (human breast cancer) and A549 (human non-small-cell lung cancer) in comparison with those of cis-[Pt(AMBi)₂Cl₂ (2) and cisplatin by means of the MTT assay. Interaction of complexes 1, 2 and cisplatin with pBR322 plasmid DNA and their restriction endonuclease reactions by BamHI and HindIII enzymes were studied by agarose gel electrophoresis. Cytotoxicity tests showed that complex 1 exhibited similar in vitro cytotoxicity profile as compared with cisplatin whereas better than corresponding cis isomer against MCF-7 and A549 human cancer cell lines. The electrophoretic mobility shift assay showed that although no comigration of the Form I and II bands of plasmid DNA was observed for complex 1 at the concentrations tested, the binding of complex 1 was able to prevent partially BamHI digestion for concentrations ranging from 40 to 160 μM while having no inhibitory effect on HindIII activity in the digestion studies with restriction enzymes. Molecular docking studies on DNA were carried out to explore the binding mode and the best orientation of the complexes 1 and 2 to DNA.

Full text of DOI:10.1016/j.molstruc.2019.02.066

Accepted Manuscript
A novel Trans-Pt(II) complex bearing 2-acetoxymethylbenzimidazole as a non-leaving
ligand (trans-[Pt(AMBi) Cl ]): Synthesis, antiproliferative activity, DNA interaction and
2
2
molecular docking studies compared with its cis isomer (cis-[Pt(AMBi) Cl ])
2
2
Gokcen Eren, Esra Emerce, Leyla Acik, Betul Aydin, Fatma Gumus
PII:
S0022-2860(19)30197-8
DOI:
https://doi.org/10.1016/j.molstruc.2019.02.066
MOLSTR 26223
Reference:
To appear in: Journal of Molecular Structure
Received Date: 1 December 2018
Revised Date: 28 January 2019
Accepted Date: 17 February 2019
Please cite this article as: G. Eren, E. Emerce, L. Acik, B. Aydin, F. Gumus, A novel Trans-Pt(II)
complex bearing 2-acetoxymethylbenzimidazole as a non-leaving ligand (trans-[Pt(AMBi) Cl ]):
2
2
Synthesis, antiproliferative activity, DNA interaction and molecular docking studies compared with its
cis isomer (cis-[Pt(AMBi) Cl ]), Journal of Molecular Structure (2019), doi: https://doi.org/10.1016/
2
2
j.molstruc.2019.02.066.
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ACCEPTED MANUSCRIPT
A Novel Trans-Pt(II) Complex Bearing 2-Acetoxymethylbenzimidazole as a Non-
leaving Ligand (trans-[Pt(AMBi) Cl ]): Synthesis, Antiproliferative Activity, DNA
2
2
Interaction and Molecular Docking Studies Compared with Its Cis Isomer (cis-
[
Pt(AMBi) Cl ])
2 2
1,
2
3
3
1
Gokcen Eren *, Esra Emerce , Leyla Acik , Betul Aydin , Fatma Gumus
1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330, Ankara,
2
Turkey Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Gazi University, 06330
Ankara, Turkey Department of Biology, Faculty of Science, Gazi University, 06500, Ankara, Turkey
3
Correspondence
Gokcen Eren,
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University,
0
+
6330, Ankara, Turkey
903122023235
gokcene@gazi.edu.tr
Abstract
Trans-[Pt(AMBi) Cl2 (1) in which AMBi is 2-acetoxymethylbenzimidazole, was
2
synthesized and characterized by spectroscopic methods. Novel complex 1 was
evaluated for its potential antiproliferative effect against three human cancer cell
lines, including HeLa (human cervix cancer), MCF-7 (human breast cancer) and
A549 (human non-small-cell lung cancer) in comparison with those of cis-
[
Pt(AMBi) Cl (2) and cisplatin by means of the MTT assay. Interaction of complexes
2 2
1
, 2 and cisplatin with pBR322 plasmid DNA and their restriction endonuclease
reactions by BamHI and HindIII enzymes were studied by agarose gel
electrophoresis. Cytotoxicity tests showed that complex 1 exhibited similar in vitro
cytotoxicity profile as compared with cisplatin whereas better than corresponding cis
isomer against MCF-7 and A549 human cancer cell lines. The electrophoretic
mobility shift assay showed that although no comigration of the Form I and II bands
of plasmid DNA was observed for complex 1 at the concentrations tested, the binding
of complex 1 was able to prevent partially BamHI digestion for concentrations
ranging from 40 to 160 ꢀM while having no inhibitory effect on HindIII activity in the
digestion studies with restriction enzymes. Molecular docking studies on DNA were
carried out to explore the binding mode and the best orientation of the complexes 1
and 2 to DNA.
Keywords
Platinum complexes, trans configuration, benzimidazole, docking, MTT, DNA binding
Introduction
Platinum complexes as antitumor agents have received considerable attention [1-6]
due to being clinically approved and have been marketed worldwide such as
cisplatin, carboplatin, oxaliplatin or marketed locally such as nedaplatin, lobaplatin
and heptaplatin for the treatment of various tumor diseases [7-10]. However, those
drugs with somewhat improved therapeutic properties but they all operate via a

ACCEPTED MANUSCRIPT
similar non-specific mechanism of action and, they exhibit most of the side effects of
cisplatin including nephrotoxicity, ototoxicity, neurotoxicity and bone marrow
suppression [11-14]. Therefore reducing the side effects and broadening the
spectrum of activity of platinum drugs still remains a field of intense research [15,16].
From the early beginning, platinum(II) complexes with trans geometry were judged to
be inactive, and the cis geometry was identified as critical for activity, therefore
largely focussed on cis-configurated platinum complexes [17-19]. However, several
platinum compounds with trans geometry have proven, in recent years, to be
antitumor active, thus disclosing a revision for the structure-activity relationships of
antitumor platinum complexes [20-29].
It is generally accepted that the main mode of action of cisplatin and other cis-
configurated platinum complexes is forming interaction with DNA resulting inhibition
of transcription. In case of trans-configurated platinum complexes, this mechanism
with different DNA binding behavior may translate into different antitumor activity
profile [30].
In designing a new platinum anticancer agent, several structural features can be
strategically modified such as modification of ammine ligands which affects the
pharmacological behavior of the drug including cell accumulation and distribution,
activation, DNA binding, and cellular responses to the DNA damage. Taking into
consideration the fact that benzimidazole ring is structurally similar to purine bases
and flexible and bulky enough to affect the kinetics and cytotoxicities of the platinum
complexes, ammine ligands which are referred to as “non-leaving group” are
replaced with 2-substitutedbenzimidazole derivatives in our previous papers in which
platinum(II) complexes with high cytotoxic activity were reported [31-35].
Herein we describe the preparation and characterization of trans-[Pt(AMBi) Cl ]
2
2
complex (1) containing 2-acetoxymethylbenzimidazole as a non-leaving ligands. We
have also investigated the trans-Pt(II) complex with regard to both antiproliferative
activity on HeLa, MCF-7 and A549 human cancer cell lines and interactions with
pBR322 plasmid DNA by agarose gel electrophoresis in relation to the cis-
[
Pt(AMBi) Cl ] complex (2) whose features have been reported previously [31] (Fig.
2 2
1
). Additionally, molecular docking studies on DNA structure were performed to
identify the binding site and binding mode of complexes 1 and 2.
Fig. 1 Chemical formulas of trans-[Pt(AMBi) Cl ] (1) and cis-[Pt(AMBi) Cl ] (2)
2
2
2
2

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Result and Discussion
Synthesis and Characterization
The general synthetic route is shown in Scheme 1. 2-Acetoxymethylbenzimidazole
(AMBi) was used as a non-leaving ligand in the structure of the Pt(II) complexes
synthesized and was prepared according to the published procedures [36]. The
synthesis of cis-[Pt(AMBi) Cl ] (2) was reported previously [31]. The synthesis
2
2
procedure for the novel trans complex, trans-[Pt(AMBi) Cl ] (1) was different from the
2
2
corresponding cis isomer. Direct substitution of chloride by AMBi at elevated
temperature was prefered for sterically demanding non-leaving ligand and the
mixture of AMBi and K PtCl (1:1.8 molar ratio) was heated at 100 °C to yield the
2
4
desired trans configuration.
Scheme 1. The general synthetic route for AmBi and complexes 1 and 2
1
Complex 1 was characterizated by elemental analysis, ESI-LC/MS, and H-NMR
spectroscopies. The numerical data are reported in the Experimental section. The
proposed formula for complex 1 was confirmed by HR ESI-MS analysis. As shown in
Fig. 2, isotopic cluster pattern of platinum in LC/MS spectra and different retention
times of cis (5.885 min) and trans (10.729 min) isomers are evidence of the purity
and the expected structure of trans-[Pt(AMBi) Cl ] (1).
2
2
Fig. 2 The LC/MS spectra of complex 1 (blue) and complex 2 (green)

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1
The H-NMR spectrum of Pt(II) complexes is indicative of complex formation. The
large downfield shift of the imidazole N1-H signal (∆δ ~ 1.25 ppm) in the spectra of
complex 1 with respect to AMBi is a result of an increase in the N1-H acid character
after platinum binding [37]. The presence of the bulky ligands in the structure of
complex has a large influence on the chemical shifts as evidenced by the multiplicity
1
of some of the signals in the H-NMR spectrum, since the rotation around the Pt-N
bound is limited.
Biological Activity Studies
The in vitro antiproliferative activity of complexes 1 and 2 was determined against a
panel of three cancer cell lines (cervix carcinoma (HeLa), breast carcinoma (MCF-7),
lung carcinoma (A549)) by MTT assay [38,39] and cisplatin was used as a reference
compound. The inhibition of cell proliferation values at 72 h are expressed as
inhibition% and are represented in Fig. 3. Compounds exhibiting inhibition of cell
viability higher than 50% have been evaluated to determine the IC values by using
50
GraphPad Prism 7.04 software which are presented in Table 1.
Fig. 3 The inhibition of cell proliferation values against a panel of three cancer cell lines at 72 h
a
Table 1. IC50 values of complexes against three human cancer cell lines
IC50 ± SD (ꢀM)
MCF-7
Complex
HeLa
A549
trans-[Pt(AMBi) Cl ] (1) 25.46 ± 3.44 30.19 ± 4.86 38.84 ± 5.27
2
2
cis-[Pt(AMBi) Cl ] (2)
21.14 ± 4.64 > 60
7.62 ± 0.58
> 100
22.14 ± 3.65 47.66 ± 10.75
2
2
Cisplatin
a
Errors are standard deviations determined from at least three independent experiments.
As shown in Fig. 3, complexes 1 and 2 exhibited comparable cytotoxic activity
against the HeLa cell line with cisplatin at 80, 40 and 20 ꢀM concentrations. Complex
1
presented similar behavior to the corresponding cis isomer 2 with a similar IC50
value at 72 h against HeLa cell line. Although both of complexes 1, 2 showed similar
inhibition effect with cisplatin at high concentrations , the calculated IC values of the
50
complexes were found to be higher than that of cisplatin, which was 7.62 ꢀM.
Compared to complex 2, complex 1 exhibited higher cytotoxicity against the MCF-7
cell line, with an IC value of 30.19 ꢀM where IC value was found to be > 60 ꢀM
50
50
for cis isomer. At high concentrations trans isomer presented comparable cytotoxic

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activity against the MCF-7 cell line with cisplatin and determined IC50 values for
complex 1 and cisplatin were found to be similar.
The cytotoxic activity results against A549 cell line showed that complex 1, the trans
isomer exhibited cytotoxic profile with an IC50 value of 38.84 ꢀM whereas the cis
complex 2 did not show appreciable cytotoxicity. On the other hand, complex 1
displayed similar antiproliferative activity with cisplatin against A549 cell line.
On the basis of these results, it can be proposed that trans configuration increases
the cytotoxic activity, whereas the corresponding cis isomer has less or similar
activity as compared to complex 1 against the cell lines tested at concentration
ranging from 5 to 80 ꢀM.
It is known that platinum based anticancer complexes interact with DNA and induce
alterations on the secondary structure of DNA such as unwinding, cross-linking or
bending DNA. Therefore, analysis of the conformational changes on DNA can
provide information about the type of adduct formation [30].
In order to investigate the impact of the complexes 1 and 2 on DNA helix,
electrophoretic mobility shift assay was carried out using pBR322 plasmid DNA on
agarose gels. Unwinding of the DNA causes a retardation of the fast running band of
the supercoiled form (Form I), whereas condensation and cross-linking of DNA
accelerates the migration of the open circular form (Form II) [30]. The electrophoretic
mobility patterns of plasmid DNA after incubation for 24 h with complexes 1, 2 and
cisplatin at various concentrations ranging from 2.5 to 160 ꢀM at are given in Fig. 4.
Fig. 4 Electrophoresis mobility shift assay for complexes 1, 2 and cisplatin. A pBR322 plasmid DNA in
was incubated with complexes 1, 2 and cisplatin for 24 h at different concentrations. C: untreated
pBR322 plasmid DNA; Lanes 1-7: Cisplatin+pBR322 plasmid DNA; Lanes 8-14: Complex 1+pBR322
plasmid DNA; Lanes 15-21: Complex 2+pBR322 plasmid DNA (Lanes 1, 8, 15: 160 ꢀM; Lanes 2, 9,
1
5
6: 80 ꢀM; Lanes 3, 10, 17: 40 ꢀM; Lanes 4, 11, 18: 20 ꢀM; Lanes 5, 12, 19: 10 ꢀM; Lanes 6, 13, 20:
ꢀM; Lanes 7, 14, 21: 2.5 ꢀM)
As shown in Fig. 4, when pBR322 plasmid DNA was interacted with increasing
concentrations of complex 2 and cisplatin, a significant decrease in mobility for the
Form I bands was observed. A decrease in the rate of migration of Form I bands is
the result of untwisting the DNA, as this reduces the number of supercoils. Complex
2
significantly modified electrophoretic mobility of both Form I and II bands and a
coalescence point of two bands which indicates a strong unwinding of the
supercoiled DNA [40] was observed similar to that of cisplatin whose bifunctional
binding shortens and condenses the DNA helix [41]. The concentrations required to
achieve total unwinding of the pBR322 plasmid DNA for complex 2 and cisplatin were
8
0 and 40 ꢀM, respectively.
Fig. 4 also suggests that for the trans configurated complex 1, no comigration of the
Form I and II bands of pBR322 plasmid DNA was observed at the concentration

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range tested. However, in the range of concentrations from 10 to 40 ꢀM the
electrophoretic mobility of Form I bands seemed to be increased slightly with respect
to untreated DNA. It has been reported that cisplatin, transplatin, and analogous
bifunctional platinum compounds coordinate to DNA in a two-step process, forming
first the monofunctional adducts preferentially at guanine residues, which
subsequently close to bifunctional lesions [42-44] and small changes in the mobility
of the Form I band of pBR322 plasmid DNA treated with some of the Pt(II) and Pd(II)
complexes containing sterically demanding non-leaving ligands were attributed to
monofunctional binding [45]. Thus, the slight increase in the mobilities of Form I band
of pBR322 plasmid DNA treated with complex 1 may be interpreted as binding of
trans configurated complex to DNA is a monofunctional manner at 10-40 ꢀM.
In order to assess whether the complexes 1, 2 and cisplatin show affinity toward
guanine-guanine (GG) and/or adenine-adenine (AA) regions, the restriction
endonuclease analysis of the complex-pBR322 plasmid DNA adducts was carried
out by BamHI and HindIII enzymes and the electrophoretograms are shown in Fig. 5.
BamHI and HindIII enzymes bind at the recognition site G↓GATCC and A↓AGCTT
and cleaves these sequences just after 5′-guanine and 5′-adenine sites, respectively,
and, as a result, convert Form I and Form II DNA to linear Form III DNA. Thus, these
enzymes were used to observe inhibition of their endonuclease activity in presence
of the complexes by blocking the recognition sites [46,47].
Fig. 5 Restriction endonuclease activity of complexes 1, 2 and cisplatin towards pBR322 plasmid
DNA. Electrophoretograms showing formation of restriction digestion products of HindIII and BamHI
enzymes on pBR322 plasmid DNA after incubation with complexes 1, 2 and cisplatin at different
concentrations. C1: untreated pBR322 plasmid DNA; C2: Enzyme+pBR322 plasmid DNA; Lanes 1-7:

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Enzyme+pBR322 plasmid DNA+complex (Lane 1: 160 ꢀM; Lane 2: 80 ꢀM; Lane 3: 40 ꢀM; Lane 4: 20
ꢀ
M; Lane 5: 10 ꢀM; Lane 6: 5 ꢀM; Lane 7: 2.5 ꢀM)
As the concentration of cisplatin increased, the HindIII and BamHI digestions were
strongly prevented. This is probably due to conformational change in the DNA
brought about by the covalent binding of cisplatin with the plasmid DNA. In case of
complexes 1 and 2, only linear Form III band was observed in the presence of HindIII
indicating that all of the plasmid DNA is doubly nicked at AA region. The cleavage
introduced in pBR322 plasmid DNA by HindIII in the presence of complexes 1 and 2
was found to be higher than BamHI at high concentrations tested. Since the amount
of the Form III is inversely related to sequence-specific binding affinity of the
complexes [48], it may be suggested that complex 2 binds more strongly with GG
region as compared to AA rich sequence. Besides, complex 1 displayed a low
amount of the supercoiled Form I band in addition to linear Form III observed at 40-
1
60 ꢀM in presence of BamHI. This observation suggested that at high
concentrations complex 1 caused little change on DNA conformation at AA rich site,
thereby the modified sequence cannot be digested completely by BamHI.
Molecular Docking Studies
The possible interaction between small molecules and DNA generally follows: (i) the
electrostatic binding with sugar-phosphate backbone, (ii) the groove binding involving
hydrogen bonding and Van der Waals interactions, (iii) intercalation with the bases
[
49,50]. In this study, complexes 1 and 2 were docked to DNA structure in order to
predict the preferred orientation of the complexes inside the DNA on the basis of
binding energies. GlideScores are calculated as -6.819 kcal/mol for complex 1 and -
5
.796 kcal/mol for complex 2. The energetically most favourable conformation of the
docked complexes revealed that complex 1 preferably interacted with the major
groove of 1BNA where complex 2 bound DNA via minor groove interactions (Fig. 6).

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Fig. 6 (A) Binding sites of complex 1 (cyan) and complex 2 (purple) in DNA. (B) Docked conformation
of complex 1 and major groove interactions. (C) Docked conformation of complex 2 and minor groove
interactions. Dashed-yellow lines represent hydrogen bonds and dashed-green lines represent π-π
interactions
As shown in Fig. 6B, complex 1 fits into the major groove through hydrogen bonds
and π-π interactions. For complex 1 three hydrogen bonds were observed between
A6, A18, G15 base pairs and imidazole N1-H, carbonyl oxygen of non-leaving ligand
AmBi. Besides, complex 1 was found to be participate in favourable π-π interactions
involving G15 and G16 ring systems.
The binding conformation and minor groove interactions of complex 2 were given in
Fig. 6C. While one of the non-leaving ligand fitted into the G/C region of the minor
groove, the other ligand is placed away from the gap. Complex 2, the cis isomer
formed two hydrogen bonds with G4 and C23 base pairs through imidazole N1-H and
carbonyl oxygen of non-leaving ligands.
It was observed that molecular docking results regarding the presence of a hydrogen
bond donor supported the necessity of the free N1-H moiety of benzimidazole-
platinum(II) complexes on the cytotoxic activity which was highlighted in our studies
previously [31]. It is well-known that the role of additional hydrogen-bonding
interactions both in the kinetics of the DNA binding process and in the stabilization of
the adduct structure is very important [51]. The potential of the complexes 1 and 2 to
form strong hydrogen bonds with DNA base pairs was also demostrated by the
results of molecular docking studies which correlated positively with antiproliferative
capacity of the compounds.

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Conclusion
A novel trans-Platinum(II) complex (1) with the formula, trans-[Pt(AMBi) Cl ] was
2
2
synthesized, characterized using elemental analysis and spectroscopic methods and
screened for its antiproliferative activity against a panel of three cancer cell lines
(cervix carcinoma (HeLa), breast carcinoma (MCF-7), lung carcinoma (A549)). For
MCF-7 and A549 cell lines, complex 1 displayed better cytotoxic activity than the
corresponding cis isomer. The interaction of the complexes 1, 2 and cisplatin with
pBR322 plasmid DNA was investigated using agarose gel electrophoresis, and the
results indicated that in constrast to complex 2 and cisplatin, the trans isomer
complex 1 displayed a weak effect on the mobility for the Form I bands at 10-40 ꢀM
compared to untreated pBR322 plasmid DNA. Digestion studies with restriction
enzymes showed that the binding of complex 1 was able to prevent partially BamHI
digestion for concentrations ranging from 40 to 160 ꢀM and had no inhibitory effect
on HindIII activity indicating higher affinity of complex 1 to AA region than GG site at
4
0-160 ꢀM. Molecular docking studies suggested that complex 1 formed favourable
hydrogen bonds and π-π interactions within the major groove of DNA resulting
energetically more stable complex and better fit than within minor groove of DNA.
The observed differences in results may suggest a differing mode of action for trans
isomer compared to that of cis isomer. The proposed explanation for the observed
configuration-based discrepancy is the formation of monoadducts and/or preference
to associate in the DNA major groove at AA regions in case of trans configuration
that contribute to antiproliferative activity. These findings represent potential for
development aimed at producing trans-platinum(II) complexes as anticancer agents,
with the idea that the difference in nature of binding with DNA may translate into an
altered spectrum of activity.
Material and Methods
Synthesis
All chemicals and solvents used were of reagent grade (Merck or Aldrich or Sigma)
and were used without further purification. Analytical thin layer chromatography
(TLC) was performed on 60 F254 precoated silica gel plates (Merck). Plates were
visualized by UV light and Dragendorff reagent.
2
-Acetoxymethylbenzimidazole (AMBi) was prepared according to already reported
procedures [36]. Synthesis and detailed structural analysis of cis-[Pt(AMBi) Cl ] (2)
2
2
were reported in our previous paper [31].
Trans-[Pt(AMBi) Cl ] (1)
2
2
2
-Acetoxymethylbenzimidazole (0.300 g, 1.6 mmol) and K PtCl (0.364 g, 0.88 mmol)
2 4
was dissolved in DMF. The reaction mixture protected from light was heated at 100
C for 7 days. A solution of 5% aqueous KCl was the n added to the solution, and the
°
mixture was stirred for 2 h. The resulting crude precipitate was filtered off and purified
by repeated washing with water, ethanol, acetone and diethyl ether and dried in
vacuo to give the required product 1 as yellowish-white powder (0.335 g, 52%); m.p.
1
>
400 °C . H-NMR (DMSO-d ): δ 13.67 (s, 2H, 2xNH), 8.36 (d, 1H, J=8.4 Hz, ArH),
6
8
.29 (d, 1H, J=7.2 Hz, ArH), 7.59 (d, 2H, J=7.6 Hz, ArH), 7.49-7.38 (m, 4H, ArH),

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5
.94 (s, 2H, -CH CO-), 5.89 (s, 2H, -CH CO-), 2.22 (d, 6H, J=3.6 Hz, 2x-
2
2
+
CH COCH ). ESI-MS: calcd. [C H Cl N O PtNa] , 669.0396; found m/z (%relative
to
2
3
20 20
2
4
4
+
the
base
peak),
669.0395
(100)
[M+Na] .
Anal.
calcd.
for
[
C H Cl N O Pt•0.4H O]: C, 36.75; H, 3.21; N, 8.57%. Found: C, 36.20; H, 3.05; N,
20 20 2 4 4 2
9
.12%.
Supporting Information
Spectroscopic Characterization, In Vitro Antiproliferative Activity and Molecular
Docking sections of Material and Methods.
Acknowledgments We are grateful to Dr. Ozgur Esim (Saglik Bilimleri University,
Gulhane Institute of Health Sciences, Ankara) and Ayhan Ibrahim Aysal (Gazi
University, Faculty of Pharmacy, Ankara) for their valuable support. We thank the
Research Foundation of Gazi University (GaziBAP-02/2012-18) for financial support.
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Trans-[Pt(AMBi) Cl (1) in which AMBi is 2-acetoxymethylbenzimidazole, was
synthesized and characterized by spectroscopic methods.
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Cytotoxicity tests showed that complex 1 exhibited similar in vitro cytotoxicity
profile as compared with cisplatin whereas better than corresponding cis
isomer against MCF-7 and A549 human cancer cell lines.