ORCID Profile
0000-0001-5231-8836
Current Organisations
University of Sussex School of Life Sciences
,
University of Sussex
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Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1CB00123J
Abstract: Fungal infections represent a global problem and there is an urgent need for new drugs. In this work, we prepared four novel organometallic derivatives of the frontline antifungal drug fluconazole with very promising in vivo activity.
Publisher: American Chemical Society (ACS)
Date: 30-03-2018
Publisher: Elsevier BV
Date: 04-2021
Publisher: MDPI AG
Date: 10-10-2023
Publisher: Wiley
Date: 03-02-2021
Publisher: Wiley
Date: 23-11-2021
Abstract: The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery c aigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally erse metal complexes for profiling as inhibitors of two relevant SARS‐CoV‐2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain‐like protease PL pro . In addition to many well‐established types of mononuclear experimental metallodrugs, the pool of compounds tested was extended to approved metal‐based therapeutics such as silver sulfadiazine and thiomersal, as well as polyoxometalates (POMs). Among the mononuclear metal complexes, only a small number of active inhibitors of the S/ACE2 interaction was identified, with titanocene dichloride as the only strong inhibitor. However, among the gold and silver containing complexes many turned out to be very potent inhibitors of PL pro activity. Highly promising activity against both targets was noted for many POMs. Selected complexes were evaluated in antiviral SARS‐CoV‐2 assays confirming activity for gold complexes with N‐heterocyclic carbene (NHC) or dithiocarbamato ligands, a silver NHC complex, titanocene dichloride as well as a POM compound. These studies might provide starting points for the design of metal‐based SARS‐CoV‐2 antiviral agents.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2016
DOI: 10.1038/NCOMMS11601
Abstract: Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism–dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5SC03115J
Abstract: High concentration crystal soaking of poised fragments and one-step elaboration identified compound 17 as an inhibitor of the PHIP(2) bromodomain.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Spencer.