Eurtivong, C, Pilkington, LI, van Rensburg, M, White, RM, Brar, HK, Rees, S, Paulin, EK, Xu, CS, Sharma, N, Leung, IKH, Leung, E, Barker, D and Reynisson, J (2019) Discovery of novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents. European Journal of Medicinal Chemistry, 187. 111919 - ?. ISSN 1768-3254

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Phosphatidylcholine-specific phospholipase C (PC-PLC) is a promising target for new anticancer treatment. Herein, we report our work in the discovery of novel drug-like PC-PLC inhibitors. Virtual screening led to the identification of promising hits from four different structural series that contain the molecular scaffold of benzenesulphonamides (10), pyrido[3,4-b]indoles (22), morpholinobenzoic acid (84) and benzamidobenzoic acid (80). 164 structural analogues were tested to investigate the chemical space around the hit series and to generate preliminary structurally activity relationships (SAR). Two of the pyrido[3,4-b]indoles (22_10 and 22_15) had comparable or better potency as D609, an established but non-drug-like PC-PLC inhibitor. Furthermore, three morpholinobenzoic acids (84, 84_4 and 84_5) had superior potency than D609. Therefore, this study paves the way towards the development of drug-like PL-PLC inhibitors as potential anticancer agents.

Item Type: Article
Additional Information: The final accepted version can be found at;
Uncontrolled Keywords: phosphatidylcholine-specific phospholipase C, drug-like, inhibitors, anticancer, agents
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Related URLs:
Depositing User: Symplectic
Date Deposited: 17 Jan 2020 09:28
Last Modified: 27 Nov 2020 01:30

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