Abstract
The cytotoxic activity of four cyclometalated platinum(II) complexes [PtMe(vpy)(L)], containing 2-vinylpyridine (vpy) and the phosphine ligands (L) PMe2Ph (1a), PPh3 (1b), PMePh2 (1c), and P(c-Hex)3 (1d), were evaluated against human breast cancer (MDA-MB-231), human lung cancer (A549), human colon cancer (SW1116), and non-tumor epithelial breast (MCF-10 A) cell lines. The highest activity was found for 1c with IC50 values of 21.10 µM, 23.36 µM, and 12.96 µM, compared to cisplatin, which was 10.12 µM, 47.57 µM, and 19.50 µM against the A549, SW1116, and MDA-MB-231 cell lines, respectively. 1a–d showed a higher selectivity index (SI) than cisplatin. Docking studies confirmed interaction to the DNA minor groove for all complexes. Genotoxicity studies on 1c showed interactions with the genomic content of malignant cells. Compared with cisplatin as a positive control, a slight shift was found in the electrophoresis mobility, which was utilized further to study the direct interaction of 1c with DNA.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Babak MV, Pfaffeneder-Kmen M, Meier-Menches SM, Legina MS, Theiner S, Licona C, Orvain C, Hejl M, Hanif M, Jakupec MA (2018) Rollover cyclometalated bipyridine platinum complexes as potent anticancer agents: impact of the ancillary ligands on the mode of action. Inorg Chem 57(5):2851–2864. https://doi.org/10.1021/acs.inorgchem.7b03210
Bauer E, Domingo X, Balcells C, Polat IH, Crespo M, Quirante J, Badía J, Baldomà L, Font-Bardia M, Cascante M (2017) Synthesis, characterization and biological activity of new cyclometallated platinum(IV) iodido complexes. Dalton Trans 46(43):14973–14987. https://doi.org/10.1039/C7DT03448B
Berenguer JR, Lalinde E, Moreno MT (2018) Luminescent cyclometalated-pentafluorophenyl PtII, PtIV and heteropolynuclear complexes. Coord Chem Rev 366:69–90. https://doi.org/10.1016/j.ccr.2018.04.002
Bergamo A, Sava G (2015) Linking the future of anticancer metal-complexes to the therapy of tumour metastases. Chem Soc Rev 44(24):8818–8835. https://doi.org/10.1039/c5cs00134j
Burger H, Loos WJ, Eechoute K, Verweij J, Mathijssen RHJ, Wiemer EAC (2011) Drug transporters of platinum-based anticancer agents and their clinical significance. Drug Resist Updates 14(1):22–34. https://doi.org/10.1016/j.drup.2010.12.002
Chi Y, Chou P-T (2010) Transition-metal phosphors with cyclometalating ligands: fundamentals and applications. Chem Soc Rev 39(2):638–655. https://doi.org/10.1039/b916237b
Dolatyari V, Shahsavari HR, Habibzadeh S, Babadi Aghakhanpour R, Paziresh S, Golbon Haghighi M, Halvagar MR (2021) Photophysical properties and kinetic studies of 2-vinylpyridine-based cycloplatinated(II) complexes containing various phosphine ligands. Molecules. https://doi.org/10.3390/molecules26072034
Ezquerro C, Sepúlveda A, Grau-Atienza A, Serrano E, Lalinde E, Berenguer JR, Garcia-Martinez J (2017) Organometallic phosphors as building blocks in sol–gel chemistry: luminescent organometallo-silica materials. J Mater Chem C 5(37):9721–9732. https://doi.org/10.1039/C7TC02188G
Farrell NP (2015) Multi-platinum anti-cancer agents. Substitution-inert compounds for tumor selectivity and new targets. Chem Soc Rev 44(24):8773–8785. https://doi.org/10.1039/c5cs00201j
Fereidoonnezhad M, Kaboudin B, Mirzaee T, Aghakhanpour B, Golbon Haghighi R, Faghih M, Faghih Z, Ahmadipour Z, Notash Z, Shahsavari B (2017a) Cyclometalated platinum(II) complexes bearing bidentate O,O′-di(alkyl)dithiophosphate ligands: photoluminescence and cytotoxic properties. Organometallics 36(9):1707–1717. https://doi.org/10.1021/acs.organomet.7b00054
Fereidoonnezhad M, Niazi M, Ahmadipour Z, Mirzaee T, Faghih Z, Faghih Z, Shahsavari HR (2017b) Cyclometalated platinum(II) complexes comprising 2-(diphenylphosphino)pyridine and various thiolate ligands: synthesis, spectroscopic characterization, and biological activity. Eur J Inorg Chem 2017(15):2247–2254. https://doi.org/10.1002/ejic.201601521
Fereidoonnezhad M, Niazi M, Shahmohammadi Beni M, Mohammadi S, Faghih Z, Faghih Z, Shahsavari HR (2017c) Synthesis, biological evaluation, and molecular docking studies on the DNA binding interactions of platinum(II) rollover complexes containing phosphorus donor ligands. ChemMedChem 12(6):456–465. https://doi.org/10.1002/cmdc.201700007
Fereidoonnezhad M, Shahsavari HR, Abedanzadeh S, Behchenari B, Hossein-Abadi M, Faghih Z, Beyzavi MH (2018a) Cycloplatinated(II) complexes bearing 1,1′-bis(diphenylphosphino)ferrocene ligand: biological evaluation and molecular docking studies. New J Chem 42(4):2385–2392. https://doi.org/10.1039/c7nj04183g
Fereidoonnezhad M, Ramezani Z, Nikravesh M, Zangeneh J, Golbon Haghighi M, Faghih Z, Faghih Z, Shahsavari HR (2018b) Cycloplatinated(II) complexes bearing an O,S-heterocyclic ligand: search for anticancer drugs. New J Chem 42(9):7177–7187. https://doi.org/10.1039/c8nj01332b
Fereidoonnezhad M, Tabaei SMH, Sakhteman A, Seradj H, Faghih Z, Faghih Z, Mojaddami A, Sadeghian B, Rezaei Z (2020) Design, synthesis, molecular docking, biological evaluations and QSAR studies of novel dichloroacetate analogues as anticancer agent. J Mol Struct 1221:128689. https://doi.org/10.1016/j.molstruc.2020.128689
Hajipour F, Mahdavinia M, Fereidoonnezhad M (2021) Half-lantern cyclometalated platinum(II) complexes as anticancer agents: molecular docking, apoptosis, cell cycle analysis and cytotoxic activity evaluations. Anticancer Agents Med Chem. https://doi.org/10.2174/1871520621666210713112105
Johnstone TC, Suntharalingam K, Lippard SJ (2016) The next generation of platinum drugs: targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chem Rev 116(5):3436–3486. https://doi.org/10.1021/acs.chemrev.5b00597
Kenny RG, Marmion CJ (2019) Toward multi-targeted platinum and ruthenium drugs—a new paradigm in cancer drug treatment regimens? Chem Rev 119(2):1058–1137. https://doi.org/10.1021/acs.chemrev.8b00271
Lalinde E, Lara R, López IP, Moreno MT, Alfaro-Arnedo E, Pichel JG, Piñeiro-Hermida S (2018) Benzothiazole-based cycloplatinated chromophores: synthetic, optical, and biological studies. Chem Eur J 24(10):2440–2456. https://doi.org/10.1002/chem.201705267
Lovejoy KS, Todd RC, Zhang S, McCormick MS, D’Aquino JA, Reardon JT, Sancar A, Giacomini KM, Lippard SJ (2008) cis-Diammine (pyridine) chloroplatinum (II), a monofunctional platinum (II) antitumor agent: uptake, structure, function, and prospects. Proc Natl Acad Sci USA 105(26):8902–8907. https://doi.org/10.1073/pnas.0803441105
Mavroidi B, Sagnou M, Stamatakis K, Paravatou-Petsotas M, Pelecanou M, Methenitis CJICA (2016) Palladium (II) and platinum (II) complexes of derivatives of 2-(4′-aminophenyl) benzothiazole as potential anticancer agents. Inorg Chim Acta 444:63–75. https://doi.org/10.1016/j.ica.2016.01.012
Messori L, Merlino A (2016) Cisplatin binding to proteins: a structural perspective. Coord Chem Rev 315:67–89. https://doi.org/10.1016/j.ccr.2016.01.010
Millán G, Giménez N, Lara R, Berenguer JsR, Moreno MT, Lalinde E, Alfaro-Arnedo E, López I, Piñeiro-Hermida S, Pichel JG (2019) Luminescent cycloplatinated complexes with biologically relevant phosphine ligands: optical and cytotoxic properties. Inorg Chem 58(2):1657–1673. https://doi.org/10.1021/acs.inorgchem.8b03211
Murphy L, Williams JG (2010) Luminescent platinum compounds: from molecules to OLEDs. Molecular organometallic materials for optics. Springer, Berlin, pp 75–111. https://doi.org/10.1007/978-3-642-01866-4_3
Nahaei A, Mandegani Z, Chamyani S, Fereidoonnezhad M, Shahsavari HR, Kuznetsov NY, Nabavizadeh SM (2022) Half-sandwich cyclometalated RhIII complexes bearing thiolate ligands: biomolecular interactions and in vitro and in vivo evaluations. Inorg Chem 61(4):2039–2056. https://doi.org/10.1021/acs.inorgchem.1c03218
Niazi M, Shahsavari HR (2016a) Cycloplatinated(II) complex bearing 2-vinylpyridine and monodentate phosphine ligands: optical properties and kinetic study. J Organomet Chem 803:82–91. https://doi.org/10.1016/j.jorganchem.2015.12.005
Niazi M, Shahsavari HR (2016b) Organoplatinum(II) complexes featuring the 2-vinylpyridine ligand. ChemistrySelect 1(8):1780–1783. https://doi.org/10.1002/slct.201600431
Omae I (2014) Applications of five-membered ring products of cyclometalation reactions as anticancer agents. Coord Chem Rev 280:84–95. https://doi.org/10.1016/j.ccr.2014.07.019
Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans 47(19):6645–6653. https://doi.org/10.1039/c8dt00838h
Sakamaki Y, Mirsadeghi A, Fereidoonnezhad H, Mirzaei M, Moghimi Dehkordi F, Chamyani Z, Alshami S, Abedanzadeh M, Shahsavar S, Beyzavi HR, M. H, (2019) Trans-platinum (II) thionate complexes: synthesis, structural characterization, and in vitro biological assessment as potent anticancer agents. ChemPlusChem 84:1525–1535. https://doi.org/10.1002/cplu.201900394
Shahsavari HR, Giménez N, Lalinde E, Moreno MT, Fereidoonnezhad M, Aghakhanpour B, Khatami R, Kalantari M, Jamshidi F, Mohammadpour Z (2019) Heterobimetallic PtII-AuI complexes comprising unsymmetrical 1,1-bis(diphenylphosphanyl)methane bridges: synthesis, photophysical, and cytotoxic studies. Eur J Inorg Chem 2019(10):1360–1373. https://doi.org/10.1002/ejic.201801297
Shahsavari HR, Hu J, Chamyani S, Sakamaki Y, Babadi Aghakhanpour R, Salmon C, Fereidoonnezhad M, Mojaddami A, Peyvasteh P, Beyzavi MH (2021) Fluorinated cycloplatinated(II) complexes bearing bisphosphine ligands as potent anticancer agents. Organometallics 40(1):72–82. https://doi.org/10.1021/acs.organomet.0c00728
Silverman AP, Bu W, Cohen SM, Lippard SJ (2002) 2.4-Å crystal structure of the asymmetric platinum complex {Pt (ammine)(cyclohexylamine)} 2 + bound to a dodecamer DNA duplex. J Biol Chem 277:49743–49749. https://doi.org/10.1074/jbc.M206979200
Taheri B, Taghavi M, Zarei M, Chamkouri N, Mojaddami A (2020) Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation. Bull Chem Soc Ethiop 34(2):377–384. https://doi.org/10.4314/bcse.v34i2.14
Wang X, Guo Z (2011) New trends and future developments of platinum-based antitumor drugs. In: Alessio E (ed) Bioorg. Med. Chem. Wiley-VCH, Weinheim, Germany, pp 97–149. https://doi.org/10.1002/9783527633104.ch4
Wang X, Wang X, Guo Z (2015) Functionalization of platinum complexes for biomedical applications. Acc Chem Res 48(9):2622–2631. https://doi.org/10.1021/acs.accounts.5b00203
Zou T, Liu J, Lum CT, Ma C, Chan RCT, Lok CN, Kwok W, Che CM (2014) Luminescent cyclometalated platinum(II) complex forms emissive intercalating adducts with double-stranded DNA and RNA: differential emissions and anticancer activities. Angew Chem Int Ed 126(38):10283–10287. https://doi.org/10.1002/anie.201405384
Zucca A, Maidich L, Carta V, Petretto GL, Stoccoro S, Agostina Cinellu M, Pilo MI, Clarkson GJ (2014) Cyclometalated complexes of platinum(II) with 2-vinylpyridine. Eur J Inorg Chem 2014(13):2278–2287. https://doi.org/10.1002/ejic.201400052
Acknowledgements
This work was supported by the Ahvaz Jundishapur University of Medical Sciences. M. F. is grateful to the Medicinal Chemistry department and Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences. The article was extracted from thesis by Ako Karimi (Grant No.CRC-9704, Ethics: IR.AJUMS.REC.1397.198).
Funding
This work is supported by Ahvaz Jundishapur University of Medical Sciences with Grant No: CRC-9704.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
Ethics: IR.AJUMS.REC.1397.198.
Research involving human and animal rights
Not applicable.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Mojaddami, A., Karimi, A., Mahdavinia, M. et al. Antiproliferative activity and DNA binding studies of cyclometalated complexes of platinum(II) containing 2-vinylpyridine. Biometals 35, 617–627 (2022). https://doi.org/10.1007/s10534-022-00392-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-022-00392-7