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

Homayon J. Arabshahi, Michelle Van Rensburg, Lisa I. Pilkington, Chae Yeon Jeon, Mirae Song, Ling Mey Gridel, Euphemia Leung, David Barker, Milena Vuica-Ross, Konstantin P. Volcho, Alexandra L. Zakharenko, Olga I. Lavrik, Jóhannes Reynisson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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 GI50 = 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 μM. 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.

Original languageEnglish (US)
Pages (from-to)1987-1997
Number of pages11
Issue number11
StatePublished - Sep 22 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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