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@article{1743081,
author = {Vanco, J. and Starha, P. and Hosek, J. and Chalupová, Marta and Suchý, Pavel and Travnicek, Z.},
article_location = {NEW YORK},
article_number = {1},
doi = {http://dx.doi.org/10.1007/s00775-019-01735-5},
keywords = {Platinum(II) complexes; Seliciclib derivatives; Antitumor activity; In vivo; Ex vivo},
language = {eng},
issn = {0949-8257},
journal = {Journal of Biological Inorganic Chemistry},
title = {Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin},
url = {https://pubmed.ncbi.nlm.nih.gov/31673793/},
volume = {25},
year = {2020}
}
TY - JOUR
ID - 1743081
AU - Vanco, J. - Starha, P. - Hosek, J. - Chalupová, Marta - Suchý, Pavel - Travnicek, Z.
PY - 2020
TI - Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin
JF - Journal of Biological Inorganic Chemistry
VL - 25
IS - 1
SP - 67-73
EP - 67-73
PB - SPRINGER
SN - 09498257
KW - Platinum(II) complexes
KW - Seliciclib derivatives
KW - Antitumor activity
KW - In vivo
KW - Ex vivo
UR - https://pubmed.ncbi.nlm.nih.gov/31673793/
L2 - https://pubmed.ncbi.nlm.nih.gov/31673793/
N2 - 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.
ER -
VANCO, J., P. STARHA, J. HOSEK, Marta CHALUPOVÁ, Pavel SUCHÝ and Z. TRAVNICEK. Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin. \textit{Journal of Biological Inorganic Chemistry}. NEW YORK: SPRINGER, 2020, vol.~25, No~1, p.~67-73. ISSN~0949-8257. Available from: https://dx.doi.org/10.1007/s00775-019-01735-5.
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