J 2020

Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin

VANCO, J., P. STARHA, J. HOSEK, Marta CHALUPOVÁ, Pavel SUCHÝ et. al.

Základní údaje

Originální název

Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin

Autoři

VANCO, J., P. STARHA, J. HOSEK, Marta CHALUPOVÁ (203 Česká republika, domácí), Pavel SUCHÝ (203 Česká republika, domácí) a Z. TRAVNICEK

Vydání

Journal of Biological Inorganic Chemistry, NEW YORK, SPRINGER, 2020, 0949-8257

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 3.358

Kód RIV

RIV/00216224:14160/20:00118186

Organizační jednotka

Farmaceutická fakulta

UT WoS

000493478200001

Klíčová slova anglicky

Platinum(II) complexes; Seliciclib derivatives; Antitumor activity; In vivo; Ex vivo

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 24. 2. 2021 13:13, doc. MVDr. Pavel Suchý, Ph.D.

Anotace

V originále

This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L-1)(2)] (1) and [Pt(ox)(L-2)(2)] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L-1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L-2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.