Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiprolifera...

Full description

Saved in:
Bibliographic Details
Published in:Organic & biomolecular chemistry 2018, Vol.16 (32), p.5859-5870
Main Authors: Blasco, Víctor, Murga, Juan, Falomir, Eva, Carda, Miguel, Royo, Santiago, Cuñat, Ana C, Sanz-Cervera, Juan F, Marco, J Alberto
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Phytogenic - chemical synthesis
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Aromatic compounds
Cell cycle
Cell Cycle - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Metathesis
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
Phosphorylation
Precursors
Stilbenes - chemical synthesis
Stilbenes - chemistry
Stilbenes - pharmacology
Tin
Tubulin - metabolism
Tumor cell lines
Tumors
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Vascular endothelial growth factor receptors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of cells in the G2/M phase in a higher percentage than combretastatin A-4 itself. Inhibition of endothelial tube formation and VEGFR-2 phosphorylation of some selected compounds is comparable to that of combretastatin A-4, particularly those of tin-containing compounds 23c and 26c, whose actions exceed those of sorafenib, a clinically used VEGFR-2 inhibitor.
ISSN:1477-0520
1477-0539
DOI:10.1039/c8ob01148f