volume 125 pages 573-585

Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies

Victor Semenov 1
Arkady A. Dudinov 1
Mikhail M. Krayushkin 1
Leonid D Konyushkin 1
Olga P Atamanenko 1
Irina B Karmanova 1
Yuri A. Strelenko 1
Boris Shor 2
Marina Semenova 3
Alex S. Kiselyov 4
Publication typeJournal Article
Publication date2017-01-01
scimago Q1
wos Q1
SJR1.142
CiteScore11.3
Impact factor5.9
ISSN02235234, 17683254
Organic Chemistry
Drug Discovery
General Medicine
Pharmacology
Abstract
A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4H)-ones 8 and 9 was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic acid esters 4a-f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an acidic medium. The targeted compounds were evaluated for their antimitotic microtubule destabilizing activity using in vivo phenotypic sea urchin embryo model and in vitro human cancer cell-based assays. Selected dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2-10 nM concentrations together with significant cytotoxicity against cancer cells including chemoresistant cell lines (IC50 in submicromolar - low nanomolar concentration range). Both approaches confirmed antimitotic microtubule destabilizing mechanism of action of the izothiazole derivatives. Structure-activity relationship study determined the importance of p-methoxybenzene A-ring for the antiproliferative effect. The most potent compound 9b containing p-methoxybenzene A-ring and thiophene B-ring caused mitotic arrest and disintegration of cell microtubules.
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GOST Copy
Semenov V. et al. Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies // European Journal of Medicinal Chemistry. 2017. Vol. 125. pp. 573-585.
GOST all authors (up to 50) Copy
Semenov V., Lichitsky B., Komogortsev A., Dudinov A. A., Krayushkin M. M., Konyushkin L. D., Atamanenko O. P., Karmanova I. B., Strelenko Y. A., Shor B., Semenova M., Kiselyov A. S. Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies // European Journal of Medicinal Chemistry. 2017. Vol. 125. pp. 573-585.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1016/j.ejmech.2016.09.075
UR - https://doi.org/10.1016/j.ejmech.2016.09.075
TI - Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies
T2 - European Journal of Medicinal Chemistry
AU - Semenov, Victor
AU - Lichitsky, Boris
AU - Komogortsev, Andrey
AU - Dudinov, Arkady A.
AU - Krayushkin, Mikhail M.
AU - Konyushkin, Leonid D
AU - Atamanenko, Olga P
AU - Karmanova, Irina B
AU - Strelenko, Yuri A.
AU - Shor, Boris
AU - Semenova, Marina
AU - Kiselyov, Alex S.
PY - 2017
DA - 2017/01/01
PB - Elsevier
SP - 573-585
VL - 125
PMID - 27718473
SN - 0223-5234
SN - 1768-3254
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2017_Semenov,
author = {Victor Semenov and Boris Lichitsky and Andrey Komogortsev and Arkady A. Dudinov and Mikhail M. Krayushkin and Leonid D Konyushkin and Olga P Atamanenko and Irina B Karmanova and Yuri A. Strelenko and Boris Shor and Marina Semenova and Alex S. Kiselyov},
title = {Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies},
journal = {European Journal of Medicinal Chemistry},
year = {2017},
volume = {125},
publisher = {Elsevier},
month = {jan},
url = {https://doi.org/10.1016/j.ejmech.2016.09.075},
pages = {573--585},
doi = {10.1016/j.ejmech.2016.09.075}
}