The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones

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.
Тип документаJournal Article
Дата публикации2018-04-25
Название журналаMolecular Diversity
ИздательSpringer Nature
ISSN13811991, 1573501X
  • Catalysis
  • Organic Chemistry
  • Drug Discovery
  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Molecular Biology
  • General Medicine
  • Information Systems
Краткое описание
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: $$\hbox {IC}_{50} = 2.20$$IC50=2.20, 2.29, 0.47 and $$3.11\,{\upmu }\hbox {M}$$3.11μM, respectively). The $$\hbox {IC}_{50}$$IC50 value of compound 4i against normal human embryonic kidney cells HEK293 was $$19.34\,{\upmu }\hbox {M}$$19.34μM, which appeared to be 6–41-fold higher than $$\hbox {IC}_{50}$$IC50 values of 4i against human cancer cells.Graphical Abstract
Пристатейные ссылки: 32
Цитируется в публикациях: 7
Synthesis and biological activity of oxindolylidene derivatives of imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazin-7-ones and imidazo[4,5-e]thiazolo[2,3-N]-1,2,4-triazin-8-ones
Izmest’ev A.N., Gazieva G.A., Kulikov A.S., Anikina L.V., Kolotyrkina N.G., Kravchenko A.N.
Q4 Russian Journal of Organic Chemistry 2017 цитирований: 5
Synthesis, reactions, and antimicrobial activity of some novel fused thiazolo[3,2-a]pyrimidine-5H-indeno[1,2-d]pyrimidine derivatives
Khalifa N.M., Nossier E.S., Al-Omar M.A., Amr A.E.
Q3 Russian Journal of General Chemistry 2016 цитирований: 9
Isatin derivatives with activity against apoptosis-resistant cancer cells
Evdokimov N.M., Magedov I.V., McBrayer D., Kornienko A.
Q2 Bioorganic and Medicinal Chemistry Letters 2016 цитирований: 21
Unexpected formation of 6-[benzofuran-3(2H)-ylidene]-3,3a,9,9a-tetra- hydroimidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazine-2,7-dione derivative
Kravchenko A.N., Vasilevskii S.V., Gazieva G.A., Nelyubina Y.V.
Q2 Mendeleev Communications 2015 цитирований: 5
Recent Advances in Chemistry of Condensed 4-Thiazolidinones
Gupta R.
Q3 Journal of Heterocyclic Chemistry 2015 цитирований: 3
Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies
Sarigol D., Uzgoren-Baran A., Tel B.C., Somuncuoglu E.I., Kazkayasi I., Ozadali-Sari K., Unsal-Tan O., Okay G., Ertan M., Tozkoparan B.
Q1 Bioorganic and Medicinal Chemistry 2015 цитирований: 64
Synthesis of imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8-diones via a rearrangement of imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7-diones in the reaction with isatins
Gazieva G.A., Izmest'ev A.N., Nelyubina Y.V., Kolotyrkina N.G., Zanin I.E., Kravchenko A.N.
Q1 RSC Advances 2015 цитирований: 7
Synthesis and biological evaluation of some novel fused thiazolo[3,2-a]pyrimidines as potential analgesic and anti-inflammatory agents
Khalifa N.M., Al-Omar M.A., Amr A.E., Baiuomy A.R., Abdel-Rahman R.F.
Q4 Russian Journal of Bioorganic Chemistry 2015 цитирований: 23
“On water” expedient synthesis of 3-indolyl-3-hydroxy oxindole derivatives and their anticancer activity in vitro
Sai Prathima P., Rajesh P., Venkateswara Rao J., Sai Kailash U., Sridhar B., Mohan Rao M.
Q1 European Journal of Medicinal Chemistry 2014 цитирований: 42
Identification of Novel Potential Antibiotics against Staphylococcus Using Structure-Based Drug Screening Targeting Dihydrofolate Reductase
Kobayashi M., Kinjo T., Koseki Y., Bourne C.R., Barrow W.W., Aoki S.
Q1 Journal of Chemical Information and Modeling 2014 цитирований: 16
Targeting Dynamic Pockets of HIV-1 Protease by Structure-Based Computational Screening for Allosteric Inhibitors
Kunze J., Todoroff N., Schneider P., Rodrigues T., Geppert T., Reisen F., Schreuder H., Saas J., Hessler G., Baringhaus K., Schneider G.
Q1 Journal of Chemical Information and Modeling 2014 цитирований: 24
Diastereoselective synthesis of (Z)-6-(2-oxo-1,2-dihydro-3H-indol-3- ylidene)-3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazin-2,7(1H, 6H)-diones
Gazieva G.A., Shishkova E.A., Kulikova L.B., Kolotyrkina N.G., Sigay N.V., Kravchenko A.N.
Q3 Journal of Heterocyclic Chemistry 2014 цитирований: 10
Cascade synthesis of the first imidazo[4,5-e]-thiazolo[2,3-c][1,2,4] triazine derivative
Kravchenko A.N., Gazieva G.A., Vasilevskii S.V., Nelyubina Y.V.
Q2 Mendeleev Communications 2014 цитирований: 8
Synthesis of New Imidazo[4,5-e][1,3]thiazolo-[3,2-b][1,2,4]triazine Derivatives
Gazieva G.A., Serkov S.A., Sigai N.V., Kostikova N.N., Nelyubina Y.V., Shishkova E.A., Kravchenko A.N.
Q3 Chemistry of Heterocyclic Compounds 2013 цитирований: 9
Autotaxin inhibition: Development and application of computational tools to identify site-selective lead compounds
Norman D.D., Ibezim A., Scott W.E., White S., Parrill A.L., Baker D.L.
Q1 Bioorganic and Medicinal Chemistry 2013 цитирований: 12
1. Gazieva G.A. и др. The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones // Molecular Diversity. 2018. Т. 22. № 3. С. 585–599.


DO - 10.1007/s11030-018-9813-8

UR -

TI - The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones

T2 - Molecular Diversity

AU - Gazieva, Galina A.

AU - Izmest’ev, Alexei N.

AU - Anikina, Lada V.

AU - Pukhov, Sergey A.

AU - Meshchaneva, Marina E.

AU - Khakimov, Dmitry V.

AU - Kolotyrkina, Natalya G.

AU - Kravchenko, Angelina N.

PY - 2018

DA - 2018/03/14

PB - Springer Science and Business Media LLC

SP - 585-599

IS - 3

VL - 22

SN - 1381-1991

SN - 1573-501X

ER -

BibTex |


doi = {10.1007/s11030-018-9813-8},

url = {},

year = 2018,

month = {mar},

publisher = {Springer Science and Business Media {LLC}},

volume = {22},

number = {3},

pages = {585--599},

author = {Galina A. Gazieva and Alexei N. Izmest'ev and Lada V. Anikina and Sergey A. Pukhov and Marina E. Meshchaneva and Dmitry V. Khakimov and Natalya G. Kolotyrkina and Angelina N. Kravchenko},

title = {The influence of substituents on the reactivity and cytotoxicity of imidazothiazolotriazinones}


Gazieva, Galina A. et al. “The Influence of Substituents on the Reactivity and Cytotoxicity of Imidazothiazolotriazinones.” Molecular Diversity 22.3 (2018): 585–599. Crossref. Web.