Antioxidant and antitumor activity of trolox, trolox succinate, and alpha-tocopheryl succinate conjugates with nitroxides

Antioxidant and antitumor activity of trolox, trolox succinate, and alpha-tocopheryl succinate conjugates with nitroxides Научная публикация

Журнал

European Journal of Medicinal Chemistry
ISSN: 0223-5234 , E-ISSN: 1768-3254

Вых. Данные

Год: 2016, Том: 122, Страницы: 127-137 Страниц : 11 DOI: 10.1016/j.ejmech.2016.05.051

Ключевые слова

Trolox; alpha-tocopheryl succinate; Antioxidants; Antitumor activity; Nitroxides

Авторы

Zakharova Ol'ga D. ¹ , Frolova Tat'yana S. ^2,3,4 , Yushkova Yuliya V. ² , Chernyak Elena I. ² , Pokrovsky Andrei G. ³ , Pokrovsky Mikhail A. ³ , Morozov Sergei V. ^2,3 , Sinitsina Ol'ga I. ⁴ , Grigor'ev Igor A. ^2,5 , Nevinsky Georgy A. ^1,3

Организации

1	(Данные Web of science) Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Div, 8 Lavrentiev Ave, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Div, NN Vorozhtsov Novosibirsk Inst Organ Chem, 9 Lavrentiev Ave, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, 2 Pirogova St, Novosibirsk 630090, Russia
4	(Данные Web of science) Russian Acad Sci, Siberian Div, Inst Cytol & Genet, 10 Lavrentiev Ave, Novosibirsk 630090, Russia
5	(Данные Web of science) EN Meshalkin State Res Inst Circulat Pathol, 15 Rechkunovskaya St, Novosibirsk 630055, Russia

A possible ability of twelve new derivatives of known antioxidants trolox (TroH), trolox succinate (TroS), alpha-tocopheryl succinate (alpha-TOS) containing nitroxyl radicals (1-12) to protect bacterial cells from spontaneous and peroxide-induced mutagenesis and their cytotoxicity against six different tumor cells as well as two normal cells were investigated and compared with that for TroH, TroS, alpha-TOH, and alpha-TOS for the first time. In contrast to TroH and TroS, all nitroxide derivatives 1-12 demonstrated not only antioxidant properties, but also suppress the growth of human tumor cells: myeloma, mammary adenocarcinoma, hepatocarcinoma, T cells leukemia, histiocytic lymphoma, and T-cellular leucosis. The IC50 values (24 - >= 300 mu M) depend significantly on the compounds and type of tumor cells. Some compounds were capable to inhibit the growth of normal mouse (LMTK) and hamster (AG17) fibroblast cells and demonstrate very different ratios in inhibition of various tumor and normal cell lines. Some nitroxide conjugates showed pronounced selectivity in suppressing the growth of several cancer cells. Overall, several compounds may be promising in parallel as antioxidants and as specific inhibitors of some tumor cells growth. Among considered spin labeled conjugates the most perspective derivatives as antioxidants and as antitumor agents are the compounds containing pyrrolidine nitroxides. In contrast to spin labeled TroH, TroS and alpha-TOS conjugates 1-12 succinyl derivatives 13-15 were inactive in inhibiting the growth of any tumor cells. It means that for suppressing the cancer cells the compounds should contain in their structures fragments of TroH, TroS or alpha-TOS. (C) 2016 Elsevier Masson SAS. All rights reserved.

Zakharova O.D. , Frolova T.S. , Yushkova Y.V. , Chernyak E.I. , Pokrovsky A.G. , Pokrovsky M.A. , Morozov S.V. , Sinitsina O.I. , Grigor'ev I.A. , Nevinsky G.A.
Antioxidant and antitumor activity of trolox, trolox succinate, and alpha-tocopheryl succinate conjugates with nitroxides
European Journal of Medicinal Chemistry. 2016. V.122. P.127-137. DOI: 10.1016/j.ejmech.2016.05.051 WOS Scopus РИНЦ

Опубликована в печати:

1 окт. 2016 г.

Web of science	WOS:000383003900011
Scopus	2-s2.0-84975887152
РИНЦ	27140321
OpenAlex	W2399975317