Synthesis, Cytotoxicity, and DNA Interactions of New Cisplatin Analogues Containing Substituted Benzimidazole Ligands

Gümüş, Fatma; Eren, Gökçen; Açık, Leyla; Çelebi, Ayten; Öztürk, Fatma; Yılmaz, Şükran; Sağkan, Rahşan İlikçi; Gür, Sibel; Özkul, Aykut; Elmalı, Ayhan; Elerman, Y.

doi:10.1021/jm8000983

Cited by 98 publications

(26 citation statements)

References 49 publications

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“…Moreover, the Pd complexes 8 and 11 are able to induce a coalescence of the two plasmid forms, an effect that has already been described for cisplatin, but at higher drug/DNAbp ratios. 73 The presence of a coalescence point indicates a strong unwinding of the pBR322 plasmid DNA for compounds 8 and 11 . The trimetallic Fe-Pd 2 compound 6 (with ligand 2 derived from DPPF) also shows a coalescence point at the lowest metal/DNA ratio (0.25, line a), most likely followed by a change of conformation of plasmid DNA from negative supercoil to positive supercoil at the highest metal compound/DNAbp ratios.…”

Section: Resultsmentioning

confidence: 99%

Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights

et al. 2013

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A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenyl-phosphanes [{Cp-P(Ph2)=N-Ph}2Fe] (1), [{Cp-P(Ph2)=N-CH2-2-NC5H4}2Fe] (2) and [{Cp-P(Ph2)=N-CH2-2-NC5H4}Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl2(3)]ClO4, [{AuCl2}2(2)](ClO4)2, [PdCl2(3)] and [{PdCl2}2(2)]. The complexes have been evaluated for their antripoliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M2Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin.

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Section: Resultsmentioning

confidence: 99%

Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights

et al. 2013

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“…When repair is incomplete, the cells will die by apoptosis. For instance, cisplatin inhibits cancer cell growth by blocking the cell cycle through the S or G 2 /M phase [30,31].…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N1,N2-dibutyl-1,2-diaminocyclohexane

Zhang

Gou

Zhao

et al. 2015

European Journal of Medicinal Chemistry

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“…In particular, the non-planar nature of benzimidazole ligands, their flexibility, and bulkiness affect the kinetics and cytotoxic properties of the corresponding metal complexes. In addition, benzimidazole-based ligands can possess N-H moiety which can facilitate DNA cleavage in cancer cells [25].…”

Section: Introductionmentioning

confidence: 99%

DNA and BSA Interaction, DNA Cleavage and In Vitro Cytotoxicity of Copper(II) Complexes: [Cu(bba)(phen)](ClO4)2 is Promising Chemotherapeutic Scaffold

Subramaniam

Murali

2020

J. Sci. Res.

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Three mononuclear copper(II) complexes of the type [Cu(bba)(bpy/phen/dpa)](ClO4)2 (1-3), where bba (N,N-bis(benzimidazol-2-ylmethyl)amine) and bpy (2,2’-bipyridine, 1) or phen (1,10-phenanthroline, 2) or dpa (2,2’-dipyridylamine, 3), have been isolated. The coordination geometry of 1 around copper(II) is square pyramidal. The electronic absorption (639-667 nm) and EPR spectral parameters (g||, ~2.25; A||, 181-186 × 10-4 cm-1; g||/A||, 122−134 cm) reveal that 1-3 possesses a square pyramidal geometry with CuN5 chromophore. Different spectral and electrochemical measurements clearly demonstrate partial intercalative interaction of 1-3 to CT DNA. Complexes strongly quench the intrinsic fluorescence of BSA through a static quenching procedure by forming BSA-(1/2/3) adducts, which are stabilized by hydrophobic interactions. The number of binding sites and binding constants were calculated. The energy transfer from BSA to Cu(II) complexes occurs with high probability. Notably, 1-3 exhibit more effective pUC 19 DNA cleavage in the presence of H2O2. Complexes 2 and 1 show remarkable cytotoxicity (IC50: 2, 2.17; 1, 8.33 mM) against human cervical carcinoma cells (HeLa) and more potent than cisplatin (IC50, 16.40 mM) while 3 exhibits less cytotoxicity (IC50, 20.82 mM). The DNA binding propensity, cleavage ability and cytotoxicity follow the order 2>1>3. Interestingly, they are non-toxic to healthy cells.

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Synthesis, Cytotoxicity, and DNA Interactions of New Cisplatin Analogues Containing Substituted Benzimidazole Ligands

Cited by 98 publications

References 49 publications

Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights

Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights

Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N1,N2-dibutyl-1,2-diaminocyclohexane

DNA and BSA Interaction, DNA Cleavage and <i>In Vitro</i> Cytotoxicity of Copper(II) Complexes: [Cu(bba)(phen)](ClO<sub>4</sub>)<sub>2</sub> is Promising Chemotherapeutic Scaffold

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