Platinum coordination compounds: synthesis and application in the treatment of oncological diseases

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Abstract

This article provides an overview of platinum-based anticancer agents. Drugs based on coordination complexes of divalent platinum Pt(II) and tetravalent platinum Pt(IV) are widely used in chemotherapeutic treatment for malignant neoplasms. The development and mechanism of action of cisplatin and its derivatives, which have been approved for clinical use, are discussed. To overcome the disadvantages of Pt (II) drugs, prodrugs based on Pt (IV) have been proposed. Approaches to modifying Pt (II) and Pt(IV) drugs to increase their selectivity for tumor cells are being discussed for future use in photodynamic therapy and photoactivated chemotherapy. The photophysical properties of platinum complexes with photosensitizers suggest the possibility of a dual effect on cancer cells. Based on the analysis of available literature data, we conclude that, despite the achieved results, further development of methods to reduce toxicity and increase selectivity while maintaining therapeutic effectiveness of drugs is necessary. Additionally, an expansion of the range of action is required. We consider combined methods of cancer treatment using platinum-based drugs, which may lead to a synergistic effect, as promising approaches.

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About the authors

N. I. Steblevskaya

Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences

Author for correspondence.
Email: steblevskaya@ich.dvo.ru
ORCID iD: 0000-0003-3114-443X
SPIN-code: 1541-9667

Dr.Sc. (Chem.), Senior Research Scientist

Russian Federation, 159 100ʰᵗ Anniversary of Vladivostok Ave., 690022, Vladivostok

M. V. Belobeletskaya

Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences

Email: rita@ich.dvo.ru
ORCID iD: 0000-0003-3705-0848
SPIN-code: 4011-0467

Ph.D. (Chem.), Senior Research Scientist

Russian Federation, 159 100ʰᵗ Anniversary of Vladivostok Ave., 690022, Vladivostok

M. A. Medkov

Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences

Email: medkov@ich.dvo.ru
ORCID iD: 0000-0002-9417-0312
SPIN-code: 8061-6645

Dr.Sc. (Chem.), Professor, Head of the Laboratory

Russian Federation, 159 100ʰᵗ Anniversary of Vladivostok Ave., 690022, Vladivostok

O. V. Shevchenko

Institute of Chemistry of the Far Eastern Branch of the Russian Academy of Sciences; Pacific State Medical University of the Ministry of Health of the Russian Federation

Email: shevchenko.ov@tgmu.ru
ORCID iD: 0000-0002-3113-3995
SPIN-code: 1714-4566

Ph.D. (Biol.), Research Scientist

Russian Federation, 159 10ʰᵗ Anniversary of Vladivostok Ave., 690022, Vladivostok; 2 Ostryakova Ave., Vladivostok, 690002

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2. Fig. 1. Platinum coordination compounds with proven efficacy and clinically approved for cancer treatment: 1 – cisplatin; 2 – carboplatin; 3 – nedaplatin; 4 – oxaliplatin; 5 – picoplatin; 6 – lobaplatin; 7 – heptaplatin; 8 – miriplatin

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3. Fig. 2. General formula of platinum antitumor drugs: L – ligands of the “non-leaving group”, nitrogen donors; X – ligands of the leaving group, displaced upon binding to DNA; R – axial ligands (in platinum (III) and (IV) complexes)

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4. Fig. 3. Platinum coordination compounds undergoing preclinical trials: dicycloplatin; 2 – phosphoplatin; 3 – phenanthriplatin; 4 – LA-12

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5. Fig. 4. Coordination compounds of Pt(IV) undergoing preclinical trials: 1 – oxoplatin; 2 – ormaplatin; 3 – iproplatin; 4 – satraplatin

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