The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones

The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones Full article

Journal

Molecular Diversity
ISSN: 1573-501X , E-ISSN: 1381-1991

Output data

Year: 2018, Volume: 22, Number: 3, Pages: 585-599 Pages count : 15 DOI: 10.1007/s11030-018-9813-8

Authors

Gazieva Galina A. ¹ , Izmest’ev Alexei N. ¹ , Anikina Lada V. ² , Pukhov Sergey A. ² , Meshchaneva Marina E. ^1,3 , Khakimov Dmitry V. ^1,4 , Kolotyrkina Natalya G. ¹ , Kravchenko Angelina N. ¹

Affiliations

1	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
2	Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Chernogolovka, Russian Federation
3	D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow, Russian Federation 125047
4	Federal State Unitary Enterprise, Keldysh Research Center, 8 Onezhskaya Str., Moscow, Russian Federation 125438

A series of tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H, 6H)-diones were synthesized via the reaction of imidazotriazinethiones and bromoacetic acid followed by condensation with isatins. Amidine skeletal rearrangement of 3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7 (1H, 6H)-diones into 1,3a,4,9a-tetrahydroimidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8 (3H, 7H)-diones under KOH treatment has been studied. The influence of substituents at positions 1,3,3a,6,9a of imidazothiazolotriazine on the ability to undergo rearrangement was analyzed based on experimental data and theoretical calculations. Both imidazothiazolo[3,2-b]triazines and their rearrangement products were evaluated for their cytotoxic activity against rhabdomyosarcoma, A549, HCT116 and MCF7 human cancer cell lines by MTT assay. Among the derivatives, 1,3-diethyl-6-[1-(2-propyl)-2-oxoindolin-3-ylidene]-3,3a,9,9a-tetrahydroimidazo [4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H, 6H)-dione 4i was found to have the highest antiproliferative activity toward the tested cell lines (4i: IC50 = 2.20, 2.29, 0.47 and 3.11μM, respectively). The IC50 value of compound 4i against normal human embryonic kidney cells HEK293 was 19.34μM, which appeared to be 6–41-fold higher than IC50 values of 4i against human cancer cells.

Gazieva G.A. , Izmest’ev A.N. , Anikina L.V. , Pukhov S.A. , Meshchaneva M.E. , Khakimov D.V. , Kolotyrkina N.G. , Kravchenko A.N.
The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones
Molecular Diversity. 2018. V.22. N3. P.585-599. DOI: 10.1007/s11030-018-9813-8 WOS Scopus OpenAlex

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