Journal
MEDCHEMCOMM
Volume 6, Issue 11, Pages 1987-1997Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5md00245a
Keywords
-
Funding
- Russian Science Foundation [14-24-00038]
- Russian Science Foundation [14-24-00038] Funding Source: Russian Science Foundation
Ask authors/readers for more resources
The anticancer activity of the thieno[2,3-b]pyridines was explored by altering the ring size of the cyclo-aliphatic moiety. Five-, six-, seven- and eight-membered derivatives were tested against the NCI60 tumour cell panel. According to this assay the most active derivative 9a has a cyclooctane moiety, which suggests that larger aliphatic ring systems are favourable. For the most sensitive tumour cell line MB-MDA-435, derivative 9a has a GI(50) = 70 nM and a LC50 = 925 nM. To explore the biological mechanism of the thieno-[2,3- b]pyridines five derivatives were tested against tyrosyl-DNA phosphodiesterase I (TDP1), a phospholipase D enzyme, using a biochemical assay. The most potent derivative for TDP1 was 9d, giving an excellent IC50 at 0.5 +/- 0.1 mu M. Also, derivative 12 was tested against 97 kinases and no or very limited activity was found, excluding this class of biomolecular targets. Finally, a mouse xenograft study using derivative 12 was encouraging but the tumour size/mass reduction was not quite statistically significant.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available