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.