New Minor Groove Covering DNA Binding Mode of Dinuclear Pt(II) Complexes with Various Pyridine-linked Bridging Ligands and Dual Anticancer-antiangiogenic Activities

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2020 Mar 13

PMID 32162071

Citations 7

Authors

Andjela A Franich

Marija D Zivkovic

Tatjana Ilic-Tomic

Ivana S dordevic

Jasmina Nikodinovic-Runic

Aleksandar Pavic

Goran V Janjic

Snezana Rajkovic

Affiliations

Soon will be listed here.

Abstract

New anticancer platinum(II) compounds simultaneously targeting tumor cells and tumor-derived neoangiogenesis, with new DNA interacting mode and large therapeutic window are appealing alternative to improve efficacy of clinical platinum chemotherapeutics. Herein, we describe three novel dinuclear [{Pt(en)Cl}(μ-L)] complexes with different pyridine-like bridging ligands (L), 4,4'-bipyridine (Pt1), 1,2-bis(4-pyridyl)ethane (Pt2) and 1,2-bis(4-pyridyl)ethene (Pt3), which highly, positively charged aqua derivatives, [{Pt(en)(HO)}(μ-L)], interact with the phosphate backbone forming DNA-Pt adducts with an unique and previously undescribed binding mode, called a minor groove covering. The results of this study suggested that the new binding mode of the aqua-Pt(II) complexes with DNA could be attributed to the higher anticancer activities of their chloride analogues. All three compounds, particularly complex [{Pt(en)Cl}(μ-4,4'-bipy)]Cl·2HO (4,4'-bipy is 4,4'-bipyridine) (Pt1), overcame cisplatin resistance in vivo in the zebrafish-mouse melanoma xenograft model, showed much higher therapeutic potential than antiangiogenic drug sunitinib malate, while effectively blocking tumor neovascularization and melanoma cell metastasis. Overall therapeutic profile showed new dinuclear Pt(II) complexes could be novel, effective and safe anticancer agents. Finally, the correlation with the structural characteristics of these complexes can serve as a useful tool for developing new and more effective anticancer drugs.

Citing Articles

Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.

Zornic S, Markovic B, Franich A, Janjic G, Jadranin M, Avdalovic J J Biol Inorg Chem. 2023; 29(1):51-73.

PMID: 38099936 DOI: 10.1007/s00775-023-02030-0.

Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes.

Kuzderova G, Rendosova M, Gyepes R, Sovova S, Sabolova D, Vilkova M Molecules. 2021; 26(21).

PMID: 34770744 PMC: 8587849. DOI: 10.3390/molecules26216335.

Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA.

Franich A, dordevic I, Zivkovic M, Rajkovic S, Janjic G, Djuran M J Biol Inorg Chem. 2021; 27(1):65-79.

PMID: 34714401 DOI: 10.1007/s00775-021-01911-6.

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments.

Czarnomysy R, Radomska D, Szewczyk O, Roszczenko P, Bielawski K Int J Mol Sci. 2021; 22(15).

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Benefits of Zebrafish Xenograft Models in Cancer Research.

Chen X, Li Y, Yao T, Jia R Front Cell Dev Biol. 2021; 9:616551.

PMID: 33644052 PMC: 7905065. DOI: 10.3389/fcell.2021.616551.

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