Synthesis and evaluation of the antiproliferative activity of new heterylmethylidene derivatives of imidazothiazolotriazinones

Synthesis and evaluation of the antiproliferative activity of new heterylmethylidene derivatives of imidazothiazolotriazinones Научная публикация

Журнал

New Journal of Chemistry
ISSN: 1369-9261 , E-ISSN: 1144-0546

Вых. Данные

Год: 2021, Том: 45, Номер: 27, Страницы: 12271-12285 Страниц : 15 DOI: 10.1039/d1nj02163j

Авторы

Izmest'ev Alexei N. ¹ , Gazieva Galina A. ¹ , Anikina Lada V. ² , Pukhov Sergey A. ² , Karnoukhova Valentina A. ³ , Kolotyrkina Natalya G. ¹ , Kravchenko Angelina N. ^1,4

Организации

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., Moscow 119991, Russian Federation
2	Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severnyi Proezd, Chernogolovka 142432, Russian Federation
3	A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova St., Moscow 119991, Russian Federation
4	Plekhanov Russian University of Economics, 36 Stremyanny Lane, Moscow 117997, Russian Federation

Two novel series of 6-heterylmethylidenetetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H,6H)-diones and 7-heterylmethylidenetetrahydroimidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8(3H,7H)-diones were synthesized by aldol condensation of tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H,6H)-dione hydrobromides with heteroaromatic aldehydes and subsequent skeletal rearrangement of the thiazolotriazine fragment. The antiproliferative activity of the synthesized compounds was evaluated. Among the derivatives, (Z)-1,3-diethyl-7-[(1H-indol-3-yl)methylidene]-1,3a,4,9a-tetrahydroimidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8(3H,7H)-dione 4n exhibited the highest antiproliferative activity. The GI50 values of the compound against 24 of the 60 cancer cell lines were < 10 nM; against 32 of the 60 cell lines, they were 11.5–63.2 nM; and the GI50 values against the remaining 4 cell lines were 1.33–6.38 μM. Experiments with annexin showed that compound 4n induced apoptosis and necrosis in Jurkat cells (acute T cell leukemia).

Izmest'ev A.N. , Gazieva G.A. , Anikina L.V. , Pukhov S.A. , Karnoukhova V.A. , Kolotyrkina N.G. , Kravchenko A.N.
Synthesis and evaluation of the antiproliferative activity of new heterylmethylidene derivatives of imidazothiazolotriazinones
New Journal of Chemistry. 2021. V.45. N27. P.12271-12285. DOI: 10.1039/d1nj02163j WOS Scopus OpenAlex

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