Recognition of arylmetylidene derivatives of imidazothiazolotriazinones as novel tubulin polymerization inhibitors

Recognition of arylmetylidene derivatives of imidazothiazolotriazinones as novel tubulin polymerization inhibitors Full article

Journal

RSC Medicinal Chemistry
ISSN: 2632-8682

Output data

Year: 2024, Volume: 15, Number: 4, Pages: 1258-1273 Pages count : 16 DOI: 10.1039/d4md00027g

Authors

Izmest'ev Alexei N ¹ , Svirshchevskaya Elena V ² , Akopov Sergey B ² , Kravchenko Angelina N ¹ , Gazieva Galina A ¹

Affiliations

1	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences Moscow 119991 Russian Federation gaz@ioc.ac.ru.
2	Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow 117997 Russian Federation esvir@mail.ibch.ru.

Two series of arylmethylidene derivatives of imidazothiazolotriazinone differing in the structure of the imidazothiazolotriazine fragment were synthesized and their antiproliferative activity and effect on tubulin polymerization were evaluated. Some of the synthesized derivatives showed a significant antiproliferative effect, among which (Z)-7-(2,4-dichlorobenzylidene)-1,3-diethyl-1,3a,4,9a-tetrahydroimidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazine-2,8(3H,7H)-dione 2n exhibited the highest antiproliferative activity. The GI50 values of the compound against 56 of the 58 cell lines were 19.4–87.8 nM; against the remaining 2 cell lines, they were 0.544–1.29 μM. Moreover, further mechanism analysis demonstrated that 2n caused G2/M arrest, induced cell apoptosis in K562 cells and blocked tubulin polymerization in the same way as colchicine.

Izmest'ev A.N. , Svirshchevskaya E.V. , Akopov S.B. , Kravchenko A.N. , Gazieva G.A.
Recognition of arylmetylidene derivatives of imidazothiazolotriazinones as novel tubulin polymerization inhibitors
RSC Medicinal Chemistry. 2024. V.15. N4. P.1258-1273. DOI: 10.1039/d4md00027g WOS Scopus OpenAlex

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