383895-84-9Relevant academic research and scientific papers
The effect of a thieno[2,3-b]pyridine PLC-γ inhibitor on the proliferation, morphology, migration and cell cycle of breast cancer cells
Leung, Euphemia,Hung, Joy M.,Barker, David,Reynisson, Johannes
, p. 99 - 106 (2014/01/06)
3-Amino-N-(3-chlorophenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b] quinoline-2-carboxamide (compound 1) is a putative phosphoinositide specific-phospholipase C-γ (PLC-γ) enzyme inhibitor. This enzyme is a plausible anticancer target linked to cell motility, important for the invasion and dissemination of tumour cells. In this work it is shown that IC50 values of compound 1 are in the low nanomolar range against a host of breast cancer cell lines as a consequence of anti-proliferative activity. These results correlate well with previously published results (Feng et al., Eur. Med. Chem., 54, 2012, 463-469) on tumour cell viability confirming the efficacy of compound 1. Flow cytometry experiments revealed that compound 1 arrests the cell cycle in the G2/M phases. Furthermore, the morphology and cell migration for the MDA-MB-231 breast cancer cell line are severely affected by administration of compound 1, which fits the hypothesis of PLC-γ inhibition. Finally, a detailed docking study against PLC reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with ligand 1 as well as a lipophilic pocket is occupied by the phenyl moiety. The results presented in this study are particularly interesting because compound 1 affects triple-negative breast cancer cells, which are difficult to treat in the clinic and are in a dire need for an effective targeted therapy. We believe that compound 1 and its thieno[2,3-b]pyridine derivatives demonstrate that such a therapy can be developed.
Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives
Hung, Joy M.,Arabshahi, Homayon J.,Leung, Euphemia,Reynisson, Jóhannes,Barker, David
, p. 420 - 437 (2015/02/19)
Forty seven thieno[2,3-b]pyridines-2-carboxamides, furo[2,3-b]pyridines-2-carboxamides and tetrahydrothieno[2,3-b]quinolones-2-carboxamides derivatives were synthesized and tested for their antiproliferative activity against the NCI-60 cell lines. The 5-keto-tetrahydrothieno[2,3-b]quinolones-2-carboxamides (series 17) were found to have the greatest activity, with the compound containing a 3-methoxyphenylcarboxamide (compound 17d) being the most active, with GI50values in the low nanomolar range against a range of cell lines, in particular the melanoma cell line MDA-MD-435 (GI50- 23 nM) and the breast cancer cell line MDA-MB-468 (GI50- 46 nM). Molecular modelling of series 17 against phosphoinositide specific-phospholipase C reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with the ligands as well as a lipophilic pocket is occupied by the phenyl carboxamide moiety.
