Synthesis, biological evaluation, and modeling studies of 1,3-disubstituted cyclobutane-containing analogs of combretastatin A4.

Autor: Malashchuk A; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine.; Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, Ukraine., Chernykh AV; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine., Hurmach VV; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine.; Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, Ukraine., Platonov MO; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine., Onopchenko O; Bienta/Enamine Ltd. (www.bienta.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine., Zozulya S; Bienta/Enamine Ltd. (www.bienta.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine., Daniliuc CG; Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany., Dobrydnev AV; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine.; Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, Ukraine., Kondratov IS; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine.; Institute of Bioorganic Chemistry & Petrochemistry, NAS of Ukraine, Murmanska Street 1, Kyiv 02660, Ukraine., Moroz YS; Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, Ukraine.; Chemspace, Ilukstes iela 38-5, Riga, LV-1082, Latvia., Grygorenko OO; Enamine Ltd. (www.enamine.net), Chervonotkatska Street 78, Kyiv 02094, Ukraine.; Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv 01601, Ukraine.
Jazyk: angličtina
Zdroj: Journal of molecular structure [J Mol Struct] 2020 Jun 15; Vol. 1210. Date of Electronic Publication: 2020 May 10.
DOI: 10.1016/j.molstruc.2020.128025
Abstrakt: With the aim of circumventing the adverse cis / trans -isomerization of combretastatin A4 (CA4), a naturally occurring tumor-vascular disrupting agent, we designed novel CA4 analogs bearing 1,3-cyclobutane moiety instead of the cis -stilbene unit of the parent compound. The corresponding cis and trans cyclobutane-containing derivatives were prepared as pure diastereomers. The structure of the target compounds was confirmed by X-ray diffraction study. The title compounds were evaluated for their cytotoxic properties in human cancer cell lines HepG2 (hepatocarcinoma) and SK-N-DZ (neuroblastoma), and the overall activity was found in micromolar range. Molecular docking studies and molecular dynamics simulation within the colchicine binding site of tubulin were in good agreement with the obtained cytotoxicity data.
Databáze: MEDLINE
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