A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues

摘要: The anticancer activity of the thieno[2,3-b]pyridines was explored by altering ring size cyclo-aliphatic moiety. Five-, six-, seven- and eight-membered derivatives were tested against NCI60 tumour cell panel. According to this assay most active derivative 9a has a cyclooctane moiety, which suggests that larger aliphatic systems are favourable. For sensitive line MB-MDA-435, GI50 = 70 nM LC50 925 nM. To explore biological mechanism five tyrosyl-DNA phosphodiesterase I (TDP1), phospholipase D enzyme, using biochemical assay. potent for TDP1 9d, giving an excellent IC50 at 0.5 ± 0.1 μM. Also, 12 97 kinases no or very limited found, excluding class biomolecular targets. Finally, mouse xenograft study encouraging but size/mass reduction not quite statistically significant.