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.

Autor: Demchuk DV; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: demchuk@ioc.ac.ru., Samet AV; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: sametav@ioc.ac.ru., Chernysheva NB; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: info@chemblock.com., Ushkarov VI; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: ushkarov@inbox.ru., Stashina GA; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: galina_stashina@chemical-block.com., Konyushkin LD; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: LeonidK@chemical-block.com., Raihstat MM; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation; Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus. Electronic address: mr@chemical-block.com., Firgang SI; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: cbi@chemical-block.com., Philchenkov AA; R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, 45 Vasyl'kivska Street, 03022 Kyiv, Ukraine. Electronic address: a_philch@onconet.kiev.ua., Zavelevich MP; R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, 45 Vasyl'kivska Street, 03022 Kyiv, Ukraine. Electronic address: butenko@onconet.kiev.ua., Kuiava LM; R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, 45 Vasyl'kivska Street, 03022 Kyiv, Ukraine. Electronic address: kuyavalm@ukr.net., Chekhun VF; R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, 45 Vasyl'kivska Street, 03022 Kyiv, Ukraine. Electronic address: chekhun@onconet.kiev.ua., Blokhin DY; Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, Moscow Region, 141700, Russia. Electronic address: blokhin@yandex.ru., Kiselyov AS; ChemDiv, 6605 Nancy Ridge Drive, San Diego, CA 92121, USA. Electronic address: akiselyov@chemdiv.com., Semenova MN; Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus; N.K. Kol'tsov Institute of Developmental Biology RAS, 26 Vavilov Street, 119334 Moscow, Russian Federation. Electronic address: ms@chemical-block.com., Semenov VV; N.D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation; Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus. Electronic address: vs@zelinsky.ru.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Jan 15; Vol. 22 (2), pp. 738-55. Date of Electronic Publication: 2013 Dec 12.
DOI: 10.1016/j.bmc.2013.12.015
Abstrakt: 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.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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