1. New manganese(II), iron(II), cobalt(II), nickel(II) and copper(II) saccharinate complexes of 2,6-bis(2-benzimidazolyl) pyridine as potential anticancer agents
- Author
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Seyma Aydinlik, Muhittin Aygün, Veysel T. Yilmaz, Ceyda Icsel, Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü., Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü., İçsel, Ceyda, Aydınlık, Şeyma, Yılmaz, Veysel Turan, ABI-2909-2020, AAI-3342-2021, and 2-s2.0-85087758658
- Subjects
Cell viability ,Protein bcl 2 ,Pyridines ,Coordination complexes ,Apoptosis ,Manganese ,IC50 ,Targeting mitochondria ,01 natural sciences ,Anticancer activity ,Saccharin ,Chemical structure ,Drug Discovery ,Antineoplastic agents ,2,6-bis(benzimidazol-2-yl)pyridine ,Enzyme activity ,Vivtro DNA-binding ,Pyridine derivative ,Cell proliferation ,Saccharin derivative ,chemistry.chemical_classification ,0303 health sciences ,Structure activity relation ,General Medicine ,Manganese derivative ,Antineoplastic agent ,Drug screening ,Molecular docking ,Dose-response relationship, drug ,Cell membrane depolarization ,Drug stability ,Human ,Saccharinate ,Double-strand breaks ,Article ,Tumor cell culture ,Metal ,03 medical and health sciences ,Drug synthesis ,Pyridine ,Dose response ,Humans ,Pharmacology ,Cisplatin ,010405 organic chemistry ,Pharmacology & pharmacy ,Tumor cells, cultured ,Copper ,0104 chemical sciences ,Drug effect ,Human cell ,Oxidative stress ,Benzimidazoles ,2,6 bis(2 benzimidazolyl)pyridine derivative ,Unclassified drug ,Enzyme activation ,Antiproliferative activity ,MCF-7 cell line ,Cobalt complex ,Cell survival ,chemistry.chemical_compound ,Nickel complex ,Synthesis ,Protein expression level ,Iron complex ,Caspase 7 ,DNA cleavage ,HT-29 cell line ,Chemistry ,Caspase 3 ,Copper complex ,Cancer-cells ,Ligand cu(II) complexes ,Plasmid DNA ,Double stranded DNA break ,Drug screening assays, antitumor ,Heavy metal ,visual_art ,A-549 cell line ,visual_art.visual_art_medium ,Tumor necrosis factor receptor superfamily member 6 ,Chemistry, medicinal ,Cobalt ,Coordination compound ,medicine.drug ,Drug cytotoxicity ,chemistry.chemical_element ,Antineoplastic metal complex ,MCF-10A cell line ,G1 phase cell cycle checkpoint ,2,6-Bis(2-benzimidazolyl)pyridine ,medicine ,Benzimidazole derivative ,DNA binding ,Mitochondrion ,030304 developmental biology ,Antineoplastic activity ,Hydrogen bond ,Reactive oxygen species ,Cytotoxic activity ,Protein Bax ,Organic Chemistry ,In vitro study ,Structure-activity relationship ,Complex ,Palladium ,2-Phenylpyridine ,Cell-cycle ,Metals, heavy ,Nickel ,Ray crystal-structure ,Structural-characterization ,Molecular structure ,Reactive oxygen metabolite ,Controlled study ,Nuclear chemistry ,First row divalent transition metals ,Mitochondrial membrane - Abstract
New mononuclear complexes [Mn(NO3)(sac)(H2O)(bzimpy)]center dot 2DMF (Mn), [Fe(sac)(2)(H2O)(bzimpy)]center dot 2H(2)O (Fe), [Co(bzimpy)(2)](sac)(2)center dot 2H(2)O (Co), [Ni(bzimpy)(2)](sac)(2)center dot H2O center dot i-PrOH (Ni) and [Cu(sac)(2)(bzimpy)]center dot 3DMF (Cu) (sac = saccharinate and bzimpy = 2,6-bis(2-benzimidazolyl)pyridine) were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS and X-ray diffraction. The anticancer activity of the metal complexes against A549 (lung), MCF-7 (breast), HT29 (colon) cancer cells and MCF10A (normal human breast epithelial) cells was tested and compared with those of cisplatin and bzimpy. The complexes displayed potent cytotoxic activity especially in MCF-7 and A549 cell lines, but they were practically inactive against the normal cells. Mechanistic studies with Mn and Cu complexes on A549 cells indicated that the complexes induced G0/G1 arrest. Both complexes increased intracellular ROS (reactive oxygen species) levels and successfully caused both mitochondrial dysfunction and doublestrand DNA breaks. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-3/7 activation and reduced Fas expression indicated that Mn and Cu induced ROS-dependent mitochondria-mediated intrinsic apoptosis in A549 cells. (C) 2020 Elsevier Masson SAS. All rights reserved.
- Published
- 2020