Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism
Научная публикация
Общая информация |
Язык:
Английский,
Жанр:
Статья (Full article),
Статус опубликования:
Опубликована,
Оригинальность:
Оригинальная
|
Журнал |
Inorganic Chemistry
ISSN: 0020-1669
, E-ISSN: 1520-510X
|
Вых. Данные |
Год: 2022,
Том: 61,
Номер: 4,
Страницы: 2105-2118
Страниц
: 14
DOI:
10.1021/acs.inorgchem.1c03314
|
Ключевые слова |
Platinum, Palladium complexes, Ligands, Genetics, Antineoplastic agents |
Авторы |
Romashev Nikolai F.
1
,
Abramov Pavel A.
1
,
Bakaev Ivan V.
1
,
Fomenko Iakov S.
1
,
Samsonenko Denis G.
1
,
Novikov Alexander S.
2
,
Tong Kelvin K.H.
3
,
Ahn Dohyun
3
,
Dorovatovskii Pavel V.
4
,
Zubavichus Yan V.
5
,
Ryadun Aleksey A.
1
,
Patutina Olga A.
6
,
Sokolov Maxim N.
1
,
Babak Maria V.
3
,
Gushchin Artem L.
1
|
Организации |
1 |
Nikolaev Institute of Inorganic Chemistry SB RAS, Novosibirsk 630090, Russia
|
2 |
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia
|
3 |
Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, Hong Kong SAR 999077, People’s Republic of China
|
4 |
National Research Center “Kurchatov Institute”, Moscow 123182, Russia
|
5 |
Boreskov Institute of Catalysis, Novosibirsk 630090, Russia
|
6 |
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia
|
|
Информация о финансировании (5)
1
|
Министерство науки и высшего образования Российской Федерации
|
FWUZ-2021-0005 (121031700313-8)
|
2
|
Министерство образования и науки Российской Федерации
|
FWUZ-2021-0002 (121031700315-2)
|
3
|
Российский научный фонд
|
21-13-00092 (121041300064-2)
|
4
|
City University of Hong Kong
|
7200682
|
5
|
City University of Hong Kong
|
9610518
|
A series of heteroleptic square-planar Pt and Pd complexes with bis(diisopropylphenyl) iminoacenaphtene (dpp-Bian) and Cl, 1,3-dithia-2-thione-4,5-dithiolate (dmit), or 1,3-dithia-2-thione-4,5-diselenolate (dsit) ligands have been prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis, and cyclic voltammetry (CV). The intermolecular noncovalent interactions in the crystal structures were assessed by density functional theory (DFT) calculations. The anticancer activity of Pd complexes in breast cancer cell lines was limited by their solubility. Pd(dpp-Bian) complexes with dmit and dsit ligands as well as an uncoordinated dpp-Bian ligand were devoid of cytotoxicity, while the [Pd(dpp-Bian)Cl2] complex was cytotoxic. On the contrary, all Pt(dpp-Bian) complexes demonstrated anticancer activity in a low micromolar concentration range, which was 8–20 times higher than the activity of cisplatin, and up to 2.5-fold selectivity toward cancer cells over healthy fibroblasts. The presence of a redox-active dpp-Bian ligand in Pt and Pd complexes resulted in the induction of reactive oxygen species (ROS) in cancer cells. In addition, these complexes were able to intercalate into DNA, indicating the dual mechanism of action.