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The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones
- 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.
- Subjects :
- Cell Survival
Apoptosis
010402 general chemistry
01 natural sciences
Medicinal chemistry
Catalysis
Inorganic Chemistry
Amidine
Jurkat Cells
chemistry.chemical_compound
Bromoacetic acid
Cell Line, Tumor
Drug Discovery
Humans
MTT assay
Reactivity (chemistry)
Physical and Theoretical Chemistry
Cytotoxicity
Molecular Biology
Cell Proliferation
Triazines
010405 organic chemistry
Chemistry
Isatin
Organic Chemistry
Imidazoles
General Medicine
0104 chemical sciences
HEK293 Cells
Aldol condensation
Human cancer
Information Systems
Subjects
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