ORCID Profile
0000-0001-8635-5897
Current Organisation
The University of Auckland
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Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.EJMECH.2019.111919
Abstract: 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.
Publisher: MDPI AG
Date: 06-01-2023
DOI: 10.3390/IJMS24021167
Abstract: Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly considered changes on the aromatic rings and at the benzylic carbons of the compounds, whilst the effects of substituents in the lactone, at the C-9′ position, have been relatively unexplored. This position has an unexploited potential for the development of novel dibenzyl butyrolactone derivatives, with previous preliminary findings revealing C-9′-hydroxymethyl analogues inducing programmed cell cycle death. Using the core structure of the bioactive natural product arctigenin, C-9′ derivatives were synthesised using various synthetic pathways and with prepared derivatives providing more potent anti-proliferative activity than the C-9′-hydroxymethyl lead compound.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0AY02208J
Abstract: In this manuscript, we report our work in the development and optimisation of a MALDI-TOF mass spectrometry assay to monitor the kinetics and inhibition of PC-PLC, a phospholipase that catalyses the hydrolysis of phosphatidylcholines.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2OB00336H
Abstract: A flexible approach to C7 keto dibenzyl butyrolactone lignans was developed and the synthesis of several natural products and their related derivatives is described herein. The developed pathway proceeds through enantioenriched β-substituted butyrolactones, from which facile aldol addition and subsequent oxidation affords the desired benzylic ketone moiety. This methodology was used to complete the first enantioselective total syntheses of three natural products, (+)-7-oxohinokinin, (+)-7-oxoarcitin and (+)-conicaol B, and a further five analogues. The utility of this method was further demonstrated through a 1-2 step modification to access another class of natural product, aryltetralin lignans, allowing the asymmetric total synthesis of (-)-isopolygamain and a polygamain derivative. Anti-proliferative testing determined (-)-isopolygamain was the most active of the compounds prepared, with IC
No related grants have been discovered for Emily Paulin.