Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elementsElectronic supplementary information (ESI) available. See DOI: 10.1039/c8ob01148f

• 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
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob01148f

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. Tricyclic compounds bearing group 14 elements have been synthesized. Effects on tumor cells, the cell cycle and VEGFR-2 have been measured.