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

Abstract

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 GI50 values 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.

Citation

Hung, J. M., Arabshahi, H. J., Leung, E., Reynisson, J., & Barker, D. (2014). Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives. European Journal of Medicinal Chemistry, 86, 420-437. https://doi.org/10.1016/j.ejmech.2014.09.001

• Journal Article Type: Article
• Acceptance Date: Sep 1, 2014
• Online Publication Date: Sep 3, 2014
• Publication Date: 2014-10
• Deposit Date: Jun 13, 2023
• Journal: European Journal of Medicinal Chemistry
• Print ISSN: 0223-5234
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 86
• Pages: 420-437
• DOI: https://doi.org/10.1016/j.ejmech.2014.09.001
• Keywords: Organic Chemistry; Drug Discovery; Pharmacology; General Medicine
• Additional Information: This article is maintained by: Elsevier; Article Title: Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives; Journal Title: European Journal of Medicinal Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejmech.2014.09.001; Content Type: article; Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.