Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines

Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines Научная публикация

Журнал

Bioorganic & Medicinal Chemistry
ISSN: 1464-3391 , E-ISSN: 0968-0896

Вых. Данные

Год: 2014, Том: 22, Номер: 2, Страницы: 738-755 Страниц : 18 DOI: 10.1016/j.bmc.2013.12.015

Авторы

Demchuk Dmitry V. ¹ , Samet Alexander V. ¹ , Chernysheva Natalia B. ¹ , Ushkarov Vladimir I. ¹ , Stashina Galina A. ¹ , Konyushkin Leonid D. ¹ , Raihstat Mikhail M. ^2,1 , Firgang Sergei I. ¹ , Philchenkov Alex A. ³ , Zavelevich Michael P. ³ , Kuiava Ludmila M. ³ , Chekhun Vasyl F. ³ , Blokhin Dmitry Yu. ⁴ , Kiselyov Alex S. ⁵ , Semenova Marina N. ^2,6 , Semenov Victor V. ^2,1

Организации

1	N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation
2	Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus
3	R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, 45 Vasyl’kivska Street, 03022 Kyiv, Ukraine
4	Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, Moscow Region, 141700, Russia
5	ChemDiv, 6605 Nancy Ridge Drive, San Diego, CA 92121, USA
6	N.K. Kol’tsov Institute of Developmental Biology RAS, 26 Vavilov Street, 119334 Moscow, Russian Federation

A series of 1,5-diaryl- and 4,5-diaryl-1,2,3-triazole derivatives of combretastatin A4 were synthesized and evaluated as antimitotic microtubule destabilizing agents using the sea urchin embryo model. Structure–activity relationship studies identified compounds substituted with 3,4,5-trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of human cancer cell lines including multi-drug resistant cells. 4,5-Diaryl-1,2,3-triazoles (C–C geometry) were found to be considerably more active than the respective 1,5-diaryl-1,2,3-triazoles (N–C geometry). Compound 10ad′ induced G2/M cell cycle arrest and apoptosis in human T-leukemia Jurkat cells via caspase 2/3/9 activation and downregulation of the antiapoptotic protein XIAP. A mitotic catastrophe has been evaluated as another possible cell death mode.

Demchuk D.V. , Samet A.V. , Chernysheva N.B. , Ushkarov V.I. , Stashina G.A. , Konyushkin L.D. , Raihstat M.M. , Firgang S.I. , Philchenkov A.A. , Zavelevich M.P. , Kuiava L.M. , Chekhun V.F. , Blokhin D.Y. , Kiselyov A.S. , Semenova M.N. , Semenov V.V.
Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines
Bioorganic & Medicinal Chemistry. 2014. V.22. N2. P.738-755. DOI: 10.1016/j.bmc.2013.12.015 WOS Scopus OpenAlex

Web of science:	WOS:000329576400008
Scopus:	2-s2.0-84892368479
OpenAlex:	W2142519216

БД	Цитирований
OpenAlex	76
Scopus	82
Web of science	76