Novel Benzimidazole- Platinum(II) Complexes: Synthesis, Characterization, Antimicrobial and Anticancer Activity

Article abstract of DOI:10.1016/j.molstruc.2020.129785

Three new Platinum complexes (1-3) with 2,6-di-tert-butyl-4-(1-phenyl-1H-benzimidazol-2-yl) phenol (L₁), N, N-dimethyl-4-(1-phenyl-1H-benzimidazol-2-yl) aniline (L₂) and 4-(1H-benzimidazol-2-yl)-N, N-dimethylaniline (L₃) w

Full text of DOI:10.1016/j.molstruc.2020.129785

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Journal Pre-proof
Novel Benzimidazole- Platinum(II) Complexes: Synthesis,
Characterization, Antimicrobial and Anticancer Activity
¨
¨
˘
Umut Dogan , Ozge Ozcan , Gizem Alaca , Aydan Arı ,
ú
Salih Gu¨nnaz , H. Tansel Yalc¸ın , Onur S¸ ahin , Sevil Iris¸li
PII:
S0022-2860(20)32098-6
DOI:
Reference:
https://doi.org/10.1016/j.molstruc.2020.129785
MOLSTR 129785
To appear in:
Journal of Molecular Structure
Received date:
Revised date:
Accepted date:
17 September 2020
2 December 2020
14 December 2020
¨
¨
˘
Please cite this article as: Umut Dogan , Ozge Ozcan , Gizem Alaca , Aydan Arı , Salih Gu¨nnaz ,
ú
H. Tansel Yalc¸ın , Onur S¸ ahin , Sevil Iris¸li , Novel Benzimidazole- Platinum(II) Complexes: Synthe-
sis, Characterization, Antimicrobial and Anticancer Activity, Journal of Molecular Structure (2020), doi:
https://doi.org/10.1016/j.molstruc.2020.129785
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier B.V.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Novel Benzimidazole- Platinum(II) Complexes: Synthesis,
Characterization, Antimicrobial and Anticancer Activity
Umut Doğana, Conceptualization, Methodology, Supervision, Project administration, Writing -
original draft, Özge Özcana, Investigation, Writing - original draft, Gizem Alacaa, Investigation,
Writing - original draft, Aydan Arıa, Investigation, Writing - original draft, Salih Günnaza,
Investigation, Writing - original draft, H. Tansel Yalçınb, Investigation, Writing - original draft,
Onur Şahinc, Investigation, Writing - original draft, Sevil İrişlia, Visualization, Software
aDepartment of Chemistry, Faculty of Science, Ege University, 35100 Bornova, Izmir, Turkey
bDepartment of Biology, Faculty of Science, Ege University, 35100 Bornova, Izmir, Turkey
cDepartment Occupational Health & Safety, School of Health, Sinop University, TR-57000 Sinop,
Turkey
GRAPHİCAL ABSTRACT(Synopsis)
New three Platinum complexes (1-3) with 2,6-di-tert-butyl-4-(1-phenyl-1H-benzimidazol-2-yl)
phenol (L1), N, N-dimethyl-4-(1-phenyl-1H-benzimidazol-2-yl) aniline (L2) and 4-(1H-
benzimidazol-2-yl)-N, N-dimethylaniline (L3) were synthesized. . The crystal structures of L1,
1 and geometrical isomer of 1 (1a) were determined by X-Ray crystallography. The cytotoxic
activities of the compounds were tested on against SHSY-5Y and U-87 cell lines and
antimicrobial effect on gram positive and gram negative bacteria .
Highlights
 New three Platinum complexes (1-3) with 2,6-di-tert-butyl-4-(1-phenyl-1H-
benzimidazol-2-yl) phenol (L1), N, N-dimethyl-4-(1-phenyl-1H-benzimidazol-2-yl)
aniline (L2) and 4-(1H-benzimidazol-2-yl)-N, N-dimethylaniline (L3) were synthesized.

The crystal structures of L1, 1 and geometrical isomer of 1 (1a) were determined by
X-Ray crystallography.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.

The cytotoxic activities of the compounds were tested on against SHSY-5Y and U-87
cell lines and antimicrobial effect on gram positive and gram negative bacteria .
Abstract
Three new Platinum complexes (1-3) with 2,6-di-tert-butyl-4-(1-phenyl-1H-benzimidazol-2-yl)
phenol (L1), N, N-dimethyl-4-(1-phenyl-1H-benzimidazol-2-yl) aniline (L2) and 4-(1H-
benzimidazol-2-yl)-N, N-dimethylaniline (L3) were prepared and characterized by FT-IR,
NMR and Elemental analyses. The crystal structures of L1, 1 and geometrical isomer of 1
(1a) were determined by X-Ray crystallography. The cytotoxic activities of the compounds
were tested on against SHSY-5Y and U-87 cell lines. The antimicrobial evaluations of the
compounds showed that they have a moderate antimicrobial effect on gram positive and
gram negative bacteria.
Keywords
benzimidazole, benzimidazole platinum (II) complexes, cytotoxicity, antimicrobial activity
1.Introduction
The use of cisplatin as one of the most active anticancer drugs is widespread. Because of
the side effects of cisplatin, such as dose-limiting toxicity, nephrotoxicity and a tendency for
tumoral drug resistance, different approaches to design new drugs, especially active organic
molecules with metal compounds, are observed [1]. Chemical modification of platinum drugs
may generate a new class of chemotherapeutic agents which have higher selectivity, limited
drug resistance and increasing cell-membrane permeability.
Platinum complexes containing imidazolic/benzimidazolic ligands [2-9] have drawn the
attention of several research groups, since imidazole/benzimidazole and their derivatives are
an important class of organic compounds. They are capable of interacting with biomolecular
targets. They also exhibit numerous activities such as antiproliferative [10] anti-inflammatory
[11,12], antiallergic [13], antibacterial [14] and antiviral [15] properties. The capability of their
scaffold is a useful structural motif for displaying chemical functionality [16]. The substituent
of the carbon atom between two nitrogen atoms in this system has effected the biological
activities [17,18].

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
In the last decade, a lof of benzimidazole – platinum complexes synthesized and reported
their antineoplastic activities on different cancer cell lines. But the reports, especially on brain
cancer cells, are limited [19,20]. Glioblastoma is a highly malignant and aggressive primary
brain tumor and can arise in children. The prognosis of glioblastoma remains very poor.
Neuroblastoma is also the most common extracranial solid cancer in children [21,22].
Cisplatin based therapy is one of the most important chemotherapy treatments for
neuroblastoma and glioblastoma, but the benefit of cisplatin is hampered by severe side
effects, including neurotoxicity and nefrotoxicity [23,24]. The limited number of coordination
compounds effective on neuroblastoma and glioblastoma [25,26] in the literature has guided
us in the synthesis of new compounds that can be used for this purpose, elucidating their
structures and determining their biological activities.
For this purpose, we report new Pt(II) – benzimidazole complexes that could prove to be
potent antitumor agents. In the present work, we have synthesized three new platinum
complexes with benzimidazole heterocycles which have different substituents at the C atom
between the two nitrogen nuclei. In a series of investigations, we have studied the
cytotoxicity of the ligands, cisplatin, [PtCl2(DMSO)(L1)], [PtCl2(DMSO)(L2)] and
[PtCl2(DMSO)(L3)] in U87 glioblastoma and SHSY-5Y neuroblastoma cell lines in vitro. We
have also examined the antimicrobial activities of the ligands and complexes.
2.Experimental
2.1. Chemicals
The reagents K2PtCl4, 3,5-Di-tert-butyl-4-hydroxybenzaldehyde, N-phenyl-o-phenylene
diamine, ethanol, dichloromethane, hexane, 4-(Dimethylamino) benzaldehyde, used in the
synthesis were commercially purchased from Merck. Pt(DMSO)2Cl2, used as starting
complex, was synthesized according to literature data [27]. The synthesis of L2 and L3 exist
in literature [28]. However, the following synthesis methods were not use catalyst.
2.2. Instrumentations