Journals / Experimed / 2022 / Volume: 12 Issue: 3

Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines

Merve Erkısa Genel(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, İSTANBUL MEDICINE PR.)0000-0002-3127-742X
Selin Selvi(İSTİNYE ÜNİVERSİTESİ, MOLEKÜLER KANSER UYGULAMA VE ARAŞTIRMA MERKEZİ)0000-0003-2762-4780
Ismail Yılmaz(KARABÜK ÜNİVERSİTESİ, FEN FAKÜLTESİ, KİMYA BÖLÜMÜ, KİMYA PR.)0000-0003-1116-0934
Remzi Okan Akar(İSTİNYE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI)0000-0001-8687-2034
İlhan Yaylım(İSTANBUL ÜNİVERSİTESİ, AZİZ SANCAR DENEYSEL TIP ARAŞTIRMA ENSTİTÜSÜ, MOLEKÜLER TIP ANABİLİM DALI)0000-0003-2615-0202
Abdurrahman Şengül(ZONGULDAK BÜLENT ECEVİT ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, KİMYA BÖLÜMÜ, KİMYA PR.)0000-0001-6851-4612
Engin Ulukaya(İSTİNYE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI)0000-0003-4875-5472
Journal
Experimed
Pages
—
Publication Date
2022-12-31
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Therefore, complex 1 deserves further attention for proof of concept in animal models.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Successful cancer treatment still requires the discovery of novel compounds that hold promise for chemotherapeutics.
📊
Key Findings & Data:Materials and Methods: A new cationic palladium(II) coordination compound, [Pd(L)]Cl2·H2O, denoted as Complex 1, where the ligand L is the compound 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine), was synthesized and characterized by the attenuated total reflectance (ATR) - fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), electrospray ionization mass spectrometry (ESI-MS), and carbon-hydrogen-nitrogen (CHN) analyses.
💡
Conclusion & Impact:Therefore, complex 1 deserves further attention for proof of concept in animal models.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Palladium complexes · N4-donor ligand · benzimidazole

Abstract

Objective: Successful cancer treatment still requires the discovery of novel compounds that hold promise for chemotherapeutics. The objective of this study was to examine the effectiveness of a newly synthesized cationic palladium(II) coordination compound that functions via several pathways to provide an efficient therapeutic option for various cancer cells. Materials and Methods: A new cationic palladium(II) coordination compound, [Pd(L)]Cl2·H2O, denoted as Complex 1, where the ligand L is the compound 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine), was synthesized and characterized by the attenuated total reflectance (ATR) - fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), electrospray ionization mass spectrometry (ESI-MS), and carbon-hydrogen-nitrogen (CHN) analyses. The density functional theory (DFT) calculations show the coordination sphere around the metal center in Complex 1 to be made up of tertiary N atoms of the pyridine (py) and benzimidazole (bim) rings completing the square-planar geometry with significant distortion. The anti-growth/cytotoxic activity of the complex was determined using the sulforhodamine B (SRB) and adenosine triphosphate (ATP) viability assays for 24 and 48 h in vitro. The study evaluates the determinations for annexin V-propidium iodide (PI) positivity, mitochondrial membrane potential loss, Bcl-2 protein inactivation, and deoxyribonucleic acid (DNA) damage to investigate the cell death mode and its partial mechanism. Results: Complex 1 caused cytotoxicity in a dose-dependent manner in all the cell lines used, with IC50 values ranging from 2.6-8.8 μM for 48 h. Among the cancer models, colon and breast cancer cell lines underwent cell death by well-described apoptosis through the intrinsic pathway involving the mitochondria. However, the other cell lines did not show such a cell death modality. This implies that differential cell death modes operate based on the cancer type. Conclusion: For the treatment of breast and colon cancers, the complex 1 appears to be a unique, promising complex. Therefore, complex 1 deserves further attention for proof of concept in animal models.

🔖

Cite This Article

Genel, M. E., Selvi, S., Yılmaz, I., Akar, R. O., Yaylım, İ., Şengül, A., Ulukaya, E. (2022). Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines. Experimed, Volume: 12 Issue: 3. https://doi.org/10.26650/experimed.1188586

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (31)

  1. Phillips MC, Mousa SA. Clinical application of nano-targeting for enhancing chemotherapeutic efficacy and safety in cancer management. Nanomedicine 2022; 17(6): 405-21. [CrossRef] google scholar
  2. Racane L, Zlatar I, Perin N, Cindric M, Radovanovic V, Banjanac M, et al. Biological Activity of Newly Synthesized Benzimidazole and Benzothizole 2, 5-Disubstituted Furane Derivatives. Molecules 2021; 26(16): 4935. [CrossRef] google scholar
  3. Roopashree B, Gayathri V, Gopi A, Devaraju KS. Syntheses, characterizations, and antimicrobial activities of binuclear ruthenium (III) complexes containing 2-substituted benzimidazole derivatives. J Coord Chem 2012; 65(22): 4023-40. [CrossRef] google scholar
  4. Renouard T, Fallahpour RA, Nazeeruddin MK, Humphry-Baker R, Gorelsky SI, Lever ABP, et al. Novel ruthenium sensitizers containing functionalized hybrid tetradentate ligands: synthesis, characterization, and INDO/S analysis. Inorg Chem 2002; 41(2): 367-78. [CrossRef] google scholar
  5. Yau HC, Chan HL, Yang M. Determination of mode of interactions between novel drugs and calf thymus DNA by using quartz crystal resonator. Sens Actuators B Chem 2002; 81(2-3): 283-88. [CrossRef] google scholar
  6. Heringova P, Kasparkova J, Brabec V. DNA adducts of antitumor cisplatin preclude telomeric sequences from forming G quadruplexes. J Biol Inorg Chem 2009; 14(6): 959-68. [CrossRef] google scholar
  7. Büyükekşi SI, Orman EB, Şengül A, Altındal A, Özkaya AR. Electrochemical and photovoltaic studies on water soluble triads: Metallosupramolecular self-assembly of ditopic bis (imidazole) perylene diimide with platinum (II)-, and palladium (II)-2, 2': 6', 2 "-terpyridyl complex ions. Dyes Pig 2017; 144: 190-202. [CrossRef] google scholar
  8. Largy E, Hamon F, Rosu F, Gabelica V, De PE, Guédin A, et al. Tridentate N-Donor Palladium (II) Complexes as Efficient Coordinating Quadruplex DNA Binders. Chemistry 2011; 17(47): 13274-283. [CrossRef] google scholar
  9. Burda JV, Zeizinger M, Leszczynski J. Activation barriers and rate constants for hydration of platinum and palladium square-planar complexes: An ab initio study. J Chem Phys 2004; 120(3): 1253-62. [CrossRef] google scholar
  10. Muller G, Bunzli, JCG, Schenk KJ, Piguet C, Hopfgartner G. Influence of bulky N-substituents on the formation of lanthanide triple helical complexes with a ligand derived from bis (benzimidazole) pyridine: structural and thermodynamic evidence. Inorg Chem 2001; 40(12): 2642-51. [CrossRef] google scholar
  11. Cusumano M, Di Pietro ML, Giannetto A. Stacking surface effect in the DNA intercalation of some polypyridine platinum (II) complexes. Inorg Chem 1999; 38(8): 1754-58. [CrossRef] google scholar
  12. Wong, ELM, Fang GS, Che CM, Zhu N. Highly cytotoxic iron (II) complexes with pentadentate pyridyl ligands as a new class of anti-tumor agents. Chem Commun 2005; (36): 4578-80. [CrossRef] google scholar
  13. Davidson JP, Faber PJ, Fischer JrRG, Mansy S, Peresie HJ, Rosenberg B, et al. " Platinum-pyrimidine blues" and related complexes: a new class of potent antitumor agents. Cancer Chemother Rep 1975; 59(2 Pt 1): 287-300. google scholar
  14. Yılmaz I, Akar OR, Erkisa M, Selvi S, Şengül A, Ulukaya E. Highly promising antitumor agent of a novel Platinum (II) complex bearing a tetradentate chelating ligand. ACS Med Chem Lett 2020; 11(5): 940-8. [CrossRef] google scholar
  15. Drew D, Doyle JR, Shaver AG. Cyclic diolefin complexes of platinum and palladium. Inorg Syn 1972; 13: 47-55. [CrossRef] google scholar
  16. Russo TV, Martin RL, Hay PJ. Density functional calculations on first-row transition metals. J Chem Phys 1994; 101(9): 7729-37. [CrossRef] google scholar
  17. Hay PJ. Methods of Electronic Structure Theory: Plenum Press, 1977. google scholar
  18. Dennington RD, Keith TA, Millam JM. GaussView 5.0, Gaussian. Inc., Wallingford, 20, 2008. google scholar
  19. Zhang IY, Wu J, Xu X. Extending the reliability and applicability of B3LYP. Chem Commun 2010; 46(18): 3057-70. [CrossRef] google scholar
  20. Czarnecki MA, Wojtkow D. Effect of varying water content on the structure of butyl alcohol/water mixtures: FT-NIR two-dimensional correlation and chemometric studies. J Mol Struct 2008; 883: 2038. [CrossRef] google scholar
  21. Yilmaz I, Acar NS, Coles SJ, Jengul A. Spectroscopic, EPR, X-ray structural, and DFT studies of the complex compound of N4-donor ligand with copper (II). J Mol Struct 2020; 1214: 128204. [CrossRef] google scholar
  22. Buyukeksi SI, Erkisa Genel M, Jengul A, Ulukaya E. Oral AY. Structural studies and cytotoxic activity of a new dinuclear coordination compound of palladium (II)-2, 2: 6, 2-terpyridine with rigid dianionic 1, 2, 4-triazole-3-sulfonate linker. Appl Organomet Chem 2018; 32(8): e4406. [CrossRef] google scholar
  23. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 1988; 37: 785-9. [CrossRef] google scholar
  24. Kohn W, Sham LJ. Self-consistent equations including exchange and correlation effects. Phys Rev 1965; 140: A1133-8. [CrossRef] google scholar
  25. Yurdakul J. Kurt M. Vibrational spectroscopic studies of metal (II) halide benzimidazole. J Mol Struct 2003; 650(1-3): 181-190. [CrossRef] google scholar
  26. Bhattacherjee A, Wategaonkar S. Water bridges anchored by a C-H. O hydrogen bond: the role of weak interactions in molecular solvation. Phys Chem Chem Phys 2016; 18(40): 2774549. [CrossRef] google scholar
  27. Miao SB, Ji BM, Deng DS, Xu C, Ma N. Crystal structures and luminescence of two zinc (II) complexes with benzimidazole ligands. J Struct Chem 2010; 51(2): 386-91. [CrossRef] google scholar
  28. Yıldız U, Şengül A, Kandemir I, Cömert F, Akkoç S, Coban B. The comparative study of the DNA binding and biological activities of the quaternized dicnq as a dicationic form and its platinum (II) heteroleptic cationic complex. Bioorg Chem 2019; 87: 70-7. [CrossRef] google scholar
  29. Kim JS, He L, Lemasters JJ. Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 2003; 304(3): 463-70. [CrossRef] google scholar
  30. Kumar A, Naaz A, Prakasham AP, Gangwar MK, Butcher RJ, Panda D, Ghosh P. Potent anticancer activity with high selectivity of a chiral palladium N-Heterocyclic Carbene Complex. ACS omega 2017; 2(8): 4632-46. [CrossRef] google scholar
  31. Bhattacherjee A, Wategaonkar S. Water bridges anchored by a C-H. O hydrogen bond: the role of weak interactions in molecular solvation. Phys Chem Chem Phys 2016; 18(40): 2774549. [CrossRef] google scholar