TRANSITION METAL ION COMPLEXES AS POTENTIAL ANTITUMOR AGENTS

1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (9-14)

AUTHOR(S) / АУТОР(И): Biljana V. Petrović

E-ADRESS / Е-АДРЕСА: biljana.petrovic@pmf.kg.ac.rs

Download Full Pdf   

DOI: 10.46793/ICCBI21.009P

ABSTRACT / САЖЕТАК:

Discovery of the antitumor activity of platinum complex, cisplatin, cis-Pt(NH3)2Cl2, and later carboplatin and oxaliplatin, led to the intensive investigation of the potential antitumor activity of the huge number of platinum complexes. Furthermore, it is well-known that platinum complexes express toxicity, numerous side effects and resistance, so the scientists make a lot of efforts to synthetize, beside Pt(II) and Pt(IV), other non-platinum compounds with potential antitumor activity, such as Pd(II), Ru(II/III) and Au(III) complexes. The goal of this study is to summarize the results of the investigation of the interactions between some mononuclear, homo- and hetero-polynuclear Pt(II), Pd(II), Ru(II/III) and Au(III) complexes with different sulfur- and nitrogen-donor biologically relevant nucleophiles. Among mononuclear complexes, the compounds with aromatic terpy (tepyridine) or bpma (bis-(2- pyridylmethyl)amine) and aliphatic dien (diethylentriamine) nitrogen-containing inert ligands were studied. Different homo- and hetero-polynuclear complexes with pz (pyrazine) or 4,4’-bipy (4,4’- bipyridine) as bridging and mostly en (ethylenediamine), bipy (2,2’-bipyridine) and dach (trans-1,2- diaminocyclohexane) as inert ligands were studied as well. The research was focused on the connection between the structure and the mechanisms of interactions with different biomolecules, such as L- cysteine                                                                   (L-Cys),

L-methionine (L-Met), tripeptide glutathione (GSH), guanosine-5’-monophosphate (5’-GMP), DNA and bovine serum albumin (BSA). Some of these complexes were selected for in vitro studies of the cytotoxicity on different tumor cell lines. Observed results contribute a lot as a guidance for the future design and determination of the structure-activity relationship (SAR) of different transition metal ion complexes.

KEY WORDS / КЉУЧНЕ РЕЧИ:

complexes, platinum, palladium, ruthenium, gold, interactions, DNA, BSA

REFERENCES / ЛИТЕРАТУРА:

  • Ž.D. Bugarčić, Bogojeski, B. Petrović, S. Hochreuther, R. van Eldik, Mechanistic studies on the reactions of platinum(II) complexes with nitrogen- and sulfur-donor biomolecules, Dalton Trans, 41 (2012) 12329-12345.
  • Ž.D. Bugarčić, J. Bogojeski, R. Van Eldik, Kinetics, mechanism and equilibrium studies on the substitution reactions of Pd(II) in reference to Pt(II) complexes with bio-molecules, Coord Chem Rev, 292 (2015) 91-106.
  • Lazarević, A. Rilak, Ž.D. Bugarčić, Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current clinical uses, cytotoxicity studies and future, Eur J Med Chem, 147 (2017) 8-31.
  • Garoufis, S. K. Hadjikakou, N. Hadjiliadis, Palladium coordination compounds as anti-viral, anti-fungal, anti-microbial and anti-tumor agents, Coord Chem Rev, 253 (2009) 1384–1397.
  • Zou, C.T. Lum, C.N. Lok, J.J. Zhang, C.M. Che, Chemical biology of anticancer gold(III) and gold(I) complexes, Chem Soc Rev, 44 (2015) 8786-8801.
  • Radisavljević, B. Petrović, Gold(III) Complexes: An Overview on Their Kinetics, Interactions With DNA/BSA, Cytotoxic Activity, and Computational Calculations, Front in Chem, 8 (2020) 379.
  • Alessio, Bioinorganic Medicinal Chemistry, Wiley-VCH Verlag & Co. KGaA, Weinheim, Germany, 2011.
  • Petrović, Doktorska disertacija, Prirodno-matematički fakultet, Kragujevac, 2005.
  • Radisavljević, A. Djeković Kesić, S. Jovanović, B. Petrovicć, Kinetics and mechanism of interactions of some monofunctional Au(III) complexes with sulphur nucleophiles, Trans Met Chem 43 (2017) 331-338.
  • Djeković, B. Petrović, Ž.D. Bugarčić, R. Puchta, R. Van Eldik, Kinetics and mechanism of the reactions of Au(III) complexes with some biologically relevant molecules, Dalton Trans, 41 (2012) 3633-3641.
  • Mijatović, B. Šmit, A. Rilak, B. Petrović, D. Čanović, Ž.D. Bugarčić, NMR kinetic studies of the interactions between [Ru(terpy)(bipy)(H2O)]2+ and some sulfur-donor ligands, Inorg ChimActa, 394 (2013) 552-557.
  • Mijatovic, R. Jelić, J. Bogojeski, Ž.D. Bugarčić, B. Petrović, Kinetics, mechanism, and equilibrium studies of the reactions between a ruthenium(II) complex and some nitrogen- and sulfur donor nucleophiles, Monatsh Chem, 144 (2013) 1489-1498.
  • Ćoćić, S. Jovanović, S. Rajković, B. Petrović, Kinetics and mechanism of the substitution reactions of dinuclear platinum (II) complexes with important bio-molecules, Inorg Chim Acta, 482 (2018) 635-642.
  • Ćoćić, S. S. Jovanović, M. Nišavić, D. Baskić, D. Todorović, S. Popović, Ž.D. Bugarčić, B. Petrović, New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity, J Inorg Biochem, 175 (2017) 67-79.
  • Jovanović, K. Obrenčević, Ž.D. Bugarčić, I. Popović, J. Žakula, B. Petrović, New bimetallic palladium(II) and platinum(II) complexes: studies of the nucleophilic substitution

reactions, interactions with CT-DNA, bovine serum albumin and cytotoxic activity, Dalton Trans, 45 (2016) 12444-12457.

  • Jovanović, B Petrović, M. Petković, Ž.D. Bugarčić, Kinetics and mechanism of substitution reactions of the new bimetallic [{PdCl(bipy)}{l-(NH2(CH2)6H2N)}{PtCl(bipy)}]Cl (ClO4) complex with important bio-molecules, Polyhedron, 101 (2015) 206-214.
  • Ćoćić, S. Jovanović-Stević, R. Jelić, S. Matić, S. Popović, P. Djurdjević, D. Baskić, B. Petrović, Homo- and hetero-dinuclear Pt(II)/Pd(II) complexes: studies of the hydrolysis, nucleophilic substitution reactions, DNA/BSA interactions, DFT calculation, molecular docking and cytotoxic activity, Dalton Trans, 49 (2020) 14411-14431.
  • Radisavljević, D. Ćoćić, S. Jovanović, B. Šmit, M. Petković, N. Milivojević, N. Planojević, S. Marković, B. Petrović, Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes, J Biol Inorg Chem, 24 (2019) 1057-1076.
  • Medjedović, A. Rilak Simović, D. Ćoćić, M. Milutinović, L. Senft, S. Blagojević, N. Milivojević, B. Petrović, Dinuclear ruthenium(II) polypyridyl complexes: Mechanistic study with biomolecules, DNA/BSA interactions and cytotoxic activity, Polyhedron, 178 (2020) 114334