Synthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNA
| Autor: | Veysel T. Yilmaz, Merve Erkisa, Muhittin Aygün, Ceyda Icsel, Engin Ulukaya, Mehmet H. Turkdemir, Omer R. Turgut |
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| Přispěvatelé: | Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü., Yılmaz, Veysel Turan, İçsel, Ceyda, Turgut, Ömer, Türkdemir, Mehmet Haluk, L-7238-2018, AAI-3342-2021, İstinye Üniversitesi, Rektörlük, Erkisa Genel, Merve, Ulukaya, Engin |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Thermal-propertirs Cytoplasm Palladium(II) Coordination complexes Drug structure Apoptosis Antiproliferative activity MCF-7 cell line 01 natural sciences Anticancer activity Cell survival chemistry.chemical_compound Synthesis HCT 116 cell line Chemical structure Annexin Drug Discovery Antineoplastic agents Fluorescent Molecular docking simulation Enzyme activity Cell proliferation Caspase 7 DNA neoplasm Crystal-structures Lipocortin 5 Platinum complex Structure activity relation Chemistry Caspase 3 Biological activity General Medicine Cancer-cells Plasmid DNA Metal-complexes Phosphine derivative Drug screening assays antitumor Mitochondria Antineoplastic agent Drug screening A-549 cell line Molecular docking Dose-response relationship drug medicine.symptom Chemistry medicinal Coordination compound Drug mechanism Human Cells cultured Saccharinate Drug cytotoxicity Stereochemistry Phosphines Antineoplastic metal complex 010402 general chemistry Article Saccharinate(2 2'-6' 2'-terpyridine)palladium(II) Drug synthesis DU145 DU145 cell line Lipophilicity Dose response medicine Structure–activity relationship Humans Mitochondrion Platinum(II) Antineoplastic activity Pharmacology 010405 organic chemistry Cell growth Pharmacology & pharmacy Organic Chemistry Agents DNA Structure-activity relationship Complex Palladium 2-Phenylpyridine 0104 chemical sciences Drug effect Mechanism of action Tertiary phosphine Human cell Cellsm in-vitro Cell culture Cisplatin Molecular structure Reactive oxygen metabolite Controlled study |
| Popis: | A series of new Pt(II) saccharinate complexes containing PR3 ligands (PPh3, PPh2Cy, PPhCy2 and PCy3) with progressive phenyl (Ph) replacement by cyclohexyl (Cy) were synthesized and structurally characterized by lR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes was tested against human breast (MCF-7), lung (A549), colon (HCT116), and prostate (DU145) cancer cell lines as well as against normal bronchial epithelial (BEAS-2B) cells. Trans-configured complexes 1, 3 and 5 emerged as potential anticancer drug candidates. The mechanism of action of the potent complexes was then investigated in detail. The three complexes interacted with DNA by groove binding and with HSA via hydrophobic IIA subdomain. Furthermore, the complexes cleaved plasmid DNA efficiently. Cellular uptake studies in MCF-7 cells showed that the biologically active complexes were mainly localized in cytoplasm. The cytotoxic activity was a function of the lipophilicity and cellular accumulation of the complexes. As determined by M30, Annexin V and Caspase 3/7 activity assays, the complexes induced apoptosis in MCF-7 and HCT116 cells. Mechanistic studies showed that the potent complexes cause excessive generation of reactive oxygen species (ROS) and display a dual action, concurrently targeting both mitochondria and genomic DNA. (C) 2018 Elsevier Masson SAS. All rights reserved. TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215Z230] The authors thank TUBITAK for the financial support given to the research project 215Z230 and are also grateful to Dr. S. Aydinlik for her help with the cellular uptake studies. WOS:000441856300048 29920455 Q1 |
| Databáze: | OpenAIRE |
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