Design, synthesis and in vitro antitumour activity of new goniofufurone and 7-epi-goniofufurone mimics with halogen or azido groups at the C-7 position
Description
A series of new antitumour lactones containing the [3.3.0] bicyclic furano-lactone core and the halogen
or azido group at the C-7 position have been designed, synthesized, and evaluated for their in vitro
antitumour activity against a panel of human tumour cell lines. Some of the analogues displayed
powerful antiproliferative effects to certain human tumour cells, but all of them were devoid of any
cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural
features of these lactones that may affect their antiproliferative activity. These are: the nature of substituent
present at the C-7 position, stereochemistry at the C-7 position, the absence of phenyl group at
the C-7 position. Flow cytometry data indicate that the cytotoxic effects of the synthesized analogues in a
culture of K562 cells are mediated by apoptosis, additionally revealing that these molecules induced
changes in cell cycle distribution of these cells. Results of Western blot analysis suggested that the most
of synthesized compounds induce apoptosis in K562 cells in caspase-dependent way.
Files
Design, synthesis and in vitro antitumour activity.pdf
Files
(1.3 MB)
| Name | Size | Download all |
|---|---|---|
|
md5:b163fa34b170173b52d12194ae48b4ff
|
1.3 MB | Preview Download |
Additional details
Related works
- Is part of
- 0223-5234 (ISSN)
Funding
- Synthesis and biological testing of new mimics or derivatives of selected cytotoxic lactones, antitumor agent tiazofurin and natural naphthenic acids 172006
- Ministry of Education, Science and Technological Development