Back to Search Start Over

The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones

Authors :
Lada V. Anikina
Dmitry V. Khakimov
S. A. Pukhov
Galina A. Gazieva
Alexei N. Izmest'ev
Marina E. Meshchaneva
Natalya G. Kolotyrkina
Angelina N. Kravchenko
Source :
Molecular Diversity. 22:585-599
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

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: $$\hbox {IC}_{50} = 2.20$$ , 2.29, 0.47 and $$3.11\,{\upmu }\hbox {M}$$ , respectively). The $$\hbox {IC}_{50}$$ value of compound 4i against normal human embryonic kidney cells HEK293 was $$19.34\,{\upmu }\hbox {M}$$ , which appeared to be 6–41-fold higher than $$\hbox {IC}_{50}$$ values of 4i against human cancer cells.

Details

ISSN :
1573501X and 13811991
Volume :
22
Database :
OpenAIRE
Journal :
Molecular Diversity
Accession number :
edsair.doi.dedup.....2a42c82e59979aef0ee5133058ae2119
Full Text :
https://doi.org/10.1007/s11030-018-9813-8