@article{dbecabd6d24a4df5ac3b9d92e20543f6,
title = "Synthesis and biological evaluation of cis-restrained carbocyclic combretastatin A-4 analogs: Influence of the ring size and saturation on cytotoxic properties",
abstract = "Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall activity of the drug candidates. Herein, we report the preparation of cis-restrained carbocyclic analogs of CA-4. The compounds, which differ by the size and hybridization of the carbocyclic ring have been evaluated for their cytotoxic properties and their ability to inhibit tubulin polymerization. Biological data, supported by molecular docking studies, identified cyclobutenyl and cyclobutyl derivatives of the natural product as highly promising drug candidates.",
keywords = "Antineoplastic Agents, Cell Line, Tumor, Drug Screening Assays, Antitumor, G2 Phase Cell Cycle Checkpoints, Humans, Molecular Docking Simulation, Molecular Structure, Protein Binding, Stilbenes, Tubulin, Tubulin Modulators, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclobut 1 enyl]phenol, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclobutyl]phenol, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclohex 1 enyl]phenol, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclohexyl]phenol, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclopent 1 en 1 yl]phenol, 2 methoxy 5 [2 (3,4,5 trimethoxyphenyl)cyclopentyl]phenol, combretastatin A4, combretastatin A4 derivative, natural product, nocodazole, paclitaxel, unclassified drug, vascular targeting agent, antineoplastic agent, fosbretabulin tromethamine, protein binding, stilbene derivative, tubulin, tubulin modulator, A-549 cell line, acute lymphoblastic leukemia, antineoplastic activity, Article, BJ [Human fibroblast] cell line, CCRF-CEM cell line, chronic myeloid leukemia, colon adenocarcinoma, controlled study, cytostasis, drug cytotoxicity, drug selectivity, drug structure, drug synthesis, fibroblast, HCT 116 cell line, human, human cell, IC50, in vitro study, K-562 cell line, lung adenocarcinoma, microtubule assembly, molecular docking, MRC-5 cell line, osteosarcoma, U2OS cell line, umbilical vein endothelial cell, chemical structure, drug effect, drug screening, G2 phase cell cycle checkpoint, metabolism, synthesis, tumor cell line",
author = "C. Nowikow and R. Fuerst and M. Kauderer and C. Dank and W. Schmid and M. Hajduch and J. Rehulka and S. Gurska and O. Mokshyna and P. Polishchuk and I. Zupk{\'o} and P. Dzubak and U. Rinner",
note = "Funding Information: This work was supported by Technology Agency of the Czech Republic TE01020028 , Ministry of Health of the Czech Republic ( 15-31984A ), internal grant of Palacky University ( IGA_LF_2019_018 ) and by the Czech Ministry of Education, Youth and Sports (LO1304, CZ-OPENSCREEN-LM2015063, EATRIS-LM2015064, IT4Innovations National Supercomputing Center – LM2015070) and the European Regional Development Fund – Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868). Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = jul,
day = "29",
doi = "10.1016/j.bmc.2019.07.048",
language = "English",
volume = "27",
journal = "Bioorg. Med. Chem.",
issn = "0968-0896",
publisher = "Elsevier Ltd",
number = "19",
}
