Alternative mechanism of action of the DNP PtIV prodrug: intracellular cisplatin release and the mitochondria-mediated apoptotic pathway

Olga Krasnovskaya; Daniil Spector; Alexander Erofeev; Peter Gorelkin; Roman Akasov; Dmitry Skvortsov; Alexander Trigub; Ksenia Vlasova; Alevtina Semkina; Nikolay Zyk; Elena Beloglazkina; Alexander Majouga

doi:10.1039/d1dt00898f

Alternative mechanism of action of the DNP Pt^IV prodrug: intracellular cisplatin release and the mitochondria-mediated apoptotic pathway

Dalton Trans. 2021 Jun 15;50(23):7922-7927. doi: 10.1039/d1dt00898f.

Authors

Affiliations

¹ Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1, 3, Moscow, 119991, Russia. [email protected] and National University of Science and Technology (MISIS), Leninskiy prospect 4, Moscow, 101000, Russia.
² I.M. Sechenov First Moscow State Medical University, Trubetskaya str. 8-2, Moscow, 119991, Russia and Federal Scientific Research Center "Crystallography and Photonics" Russian Academy of Sciences, Leninskiy Prospect 59, Moscow, 119333, Russia.
³ Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1, 3, Moscow, 119991, Russia. [email protected] and Faculty of biology and biotechnologies, Higher School of Economics, Myasnitskaya 13, Moscow, 101000, Russia.
⁴ National Research Center "Kurchatov Institute", Akademika Kurchatova pl., 1, Moscow, 123182, Russia.
⁵ Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1, 3, Moscow, 119991, Russia. [email protected].
⁶ Pirogov Russian National Research Medical University (RNRMU), Ostrovitianov str. 1, Moscow, 117997, Russia and Serbsky National Medical Research Center for Psychiatry and Narcology, Department of Basic and Applied Neurobiology, Kropotkinskiy 23, Moscow 119991, Russia.
⁷ Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1, 3, Moscow, 119991, Russia. [email protected] and National University of Science and Technology (MISIS), Leninskiy prospect 4, Moscow, 101000, Russia and Mendeleev University of Chemical Technology of Russia, Miusskaya Ploshchad' 9, Moscow, 125047, Russia.

PMID: 34037020
DOI: 10.1039/d1dt00898f

Abstract

In a recent research paper Dr. Suxing Jin et al. reported two multispecific PtIV complexes DNP and NP with non-steroidal anti-inflammatory drug naproxen (NPX) as the axial ligand(s). Herein, we clarify the mechanism of action of DNP, its therapeutic target and intracellular redox-status.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Proliferation / drug effects
Cell Survival / drug effects
Cisplatin / chemistry
Cisplatin / pharmacology*
Drug Screening Assays, Antitumor
Humans
Mitochondria / drug effects*
Mitochondria / metabolism
Molecular Structure
Organoplatinum Compounds / chemical synthesis
Organoplatinum Compounds / chemistry
Organoplatinum Compounds / pharmacology*
Prodrugs / chemical synthesis
Prodrugs / chemistry
Prodrugs / pharmacology*
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Organoplatinum Compounds
Prodrugs
Cisplatin