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Open AccessAbstract

Development of Thienopyridines as Potent Antiproliferative Agents

School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand
School of Pharmacy, Keele University, Staffordshire ST5 5BG, UK
Author to whom correspondence should be addressed.
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
Proceedings 2019, 22(1), 2;
Published: 6 August 2019
(This article belongs to the Proceedings of The Molecules Medicinal Chemistry Symposium)
PDF [127 KB, uploaded 6 August 2019]


Virtual high throughput screening of a large compound library against the regulatory enzyme phospholipase C (PLC) led to the discovery of the thieno[2,3-b]pyridine-2-carboxamides as potential inhibitors. Subsequent biological testing verified the antiproliferative activity of this compound class. Morphology and motility assays, using a number of triple negative breast cancer cell lines, led to the conclusion that PLC is the most probable biomolecular target. Using a combination of computer-aided drug design and synthesis, further analogues have been prepared and tested for their antiproliferative activity, allowing a comprehensive SAR to be developed. Numerous analogues with low nano-molar growth inhibition against various cancers have been prepared. SAR studies suggest that the core structure can be fine-tuned to specific cancers, potentially due to enzyme/isoform specificity. Additionally, mouse xenograft assays showed significant reduction in tumour size after treatment, whilst showing no adverse effects to non-cancerous mice. Here, we report on our recent development of novel thienopyridines and derivatives, expanding the SAR against PLC, and our efforts to prepare potent, soluble, and bioavailable compounds.
Keywords: thienopyridine; antiproliferative; Phospholipase C; SAR study thienopyridine; antiproliferative; Phospholipase C; SAR study
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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MDPI and ACS Style

Barker, D.; Pilkington, L.I.; Haverkate, N.; Leung, E.; Reynisson, J. Development of Thienopyridines as Potent Antiproliferative Agents. Proceedings 2019, 22, 2.

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