Highly selective antitumor agents: Manganese(II) complexes with 2,2′-bipyridine / 1,10-phenanthroline and tetrazolate derivatives exhibiting exceptional activity against lung adenocarcinoma

Highly selective antitumor agents: Manganese(II) complexes with 2,2′-bipyridine / 1,10-phenanthroline and tetrazolate derivatives exhibiting exceptional activity against lung adenocarcinoma Научная публикация

Журнал

Journal of Molecular Structure
ISSN: 0022-2860

Вых. Данные

Год: 2026, Том: 1372, Номер статьи : 146650, Страниц : 18 DOI: 10.1016/j.molstruc.2026.146650

Ключевые слова

Manganese(II) complexes; Cytotoxicity; Reactive oxygen species; DNA binding; BSA binding; Molecular docking

Авторы

Ermakova Ekaterina A. ¹ , Golubeva Yuliya A. ¹ , Smirnova Ksenia S. ¹ , Klyushova Lyubov S. ² , Romashev Nikolay F. ¹ , Komlyagina Veronika I. ¹ , Osik Nataliya A. ³ , Lider Elizaveta V. ¹

Организации

1	Nikolaev Institute of Inorganic Chemistry SB RAS, Novosibirsk, Russia
2	Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine (IMBB FRC FTM), Novosibirsk, Russia
3	International Tomography Center SB RAS, Novosibirsk, Russia

A series of ten mononuclear manganese(II) complexes based on 5-(4-chlorophenyl)-1H-tetrazole (HL) and various N,N'-chelating agents (2,2′-bipyridine, 1,10-phenanthroline, and their derivatives) were synthesized and characterized by single-crystal XRD, UV–vis and FTIR spectroscopy, conductometry, and mass spectrometry. The 5-(4-chlorophenyl)-1H-tetrazolate anion coordinates in a monodentate mode via the N2 atom or acts as an outer-sphere counterion, depending on the reaction stoichiometry and the nature of the chelator. Two complexes bearing 1,10-phenanthroline-5,6‑dione (phendione), namely 6 and 9, exhibited the highest cytotoxicity against a panel of 2D human tumor cell lines (Hep2, HepG2, MCF7, A549, SK-LU-1), with LC₅₀ values in the low micromolar range and selectivity indices of 48 and 4 toward SK-LU-1 and A549 lung adenocarcinoma cells, respectively. The antiproliferative effect is mediated by mitochondria-independent ROS overproduction (up to 4-fold increase) and inhibition of tumor cell migration. Both complexes showed moderate BSA binding affinity and interacted with DNA, as confirmed by spectroscopic methods and molecular docking. Cyclic voltammetry revealed that complex 6, bearing an inner-sphere tetrazolate ligand, retains structural integrity upon reduction, whereas complex 9 undergoes irreversible decomposition with loss of phendione ligands. This redox stability distinguishes complex 6 as a promising manganese-based antitumor scaffold.

Ermakova E.A. , Golubeva Y.A. , Smirnova K.S. , Klyushova L.S. , Romashev N.F. , Komlyagina V.I. , Osik N.A. , Lider E.V.
Highly selective antitumor agents: Manganese(II) complexes with 2,2′-bipyridine / 1,10-phenanthroline and tetrazolate derivatives exhibiting exceptional activity against lung adenocarcinoma
Journal of Molecular Structure. 2026. V.1372. 146650 :1-18. DOI: 10.1016/j.molstruc.2026.146650 WOS Scopus OpenAlex

Поступила в редакцию:	23 мар. 2026 г.
Принята к публикации:	22 мая 2026 г.
Опубликована online:	23 мая 2026 г.
Опубликована в печати:	15 окт. 2026 г.

≡ Web of science:	WOS:001784964600001
≡ Scopus:	2-s2.0-105040615009
≡ OpenAlex:	W7162191363