期刊
JOURNAL OF MOLECULAR STRUCTURE
卷 1210, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.molstruc.2020.128025
关键词
Combretastatin; Tubulin; Molecular dynamics; Conformational restriction; Cyclobutane
资金
- Enamine Ltd.
- NIH [GM133836]
- Ministry of Education and Science of Ukraine [19BF037-03]
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-disubstituted 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. (C) 2020 Elsevier B.V. All rights reserved.
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