Michael J. Delves
YOU?
Author Swipe
View article: Correction: Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials
Correction: Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials Open
[This corrects the article DOI: 10.1371/journal.ppat.1011711.].
View article: Targeting Aurora Kinases as Essential Cell‐Cycle Regulators to Deliver Multi‐Stage Antimalarials Against <i>Plasmodium Falciparum</i>
Targeting Aurora Kinases as Essential Cell‐Cycle Regulators to Deliver Multi‐Stage Antimalarials Against <i>Plasmodium Falciparum</i> Open
Kinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nucle…
View article: Targeting Aurora Kinases as Essential Cell‐Cycle Regulators to Deliver Multi‐Stage Antimalarials Against <i>Plasmodium Falciparum</i>
Targeting Aurora Kinases as Essential Cell‐Cycle Regulators to Deliver Multi‐Stage Antimalarials Against <i>Plasmodium Falciparum</i> Open
Kinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nucle…
View article: Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites
Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites Open
Drug resistance is steadily undermining the efficacy of frontline anti-malarials, highlighting the urgent need for novel therapies with alternative mechanisms of action. The chemical addition of different moieties to azithromycin yields co…
View article: Optimization and Characterization of the Antimalarial Activity of <i>N</i>-Aryl Acetamides that are Susceptible to Mutations in ROM8 and CSC1
Optimization and Characterization of the Antimalarial Activity of <i>N</i>-Aryl Acetamides that are Susceptible to Mutations in ROM8 and CSC1 Open
New antimalarials are needed due to the threat of emerging resistance against existing antimalarial therapies. A phenotypic screen uncovered the N-aryl acetamide class that inhibits the development of P. falciparum asexual ring-stage paras…
View article: Targeting Aurora kinases as essential cell cycle regulators to deliver multi-stage antimalarials against <i>Plasmodium falciparum</i>
Targeting Aurora kinases as essential cell cycle regulators to deliver multi-stage antimalarials against <i>Plasmodium falciparum</i> Open
Kinases that play critical roles in the development and adaptation of Plasmodium falciparum present novel opportunities for chemotherapeutic intervention. Of particular interest are mitotic kinases that regulate the proliferation of the pa…
View article: Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4
Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4 Open
To discover new antimalarials, a screen of the Janssen Jumpstarter library against Plasmodium falciparum uncovered the N-acetamide indole hit class. The structure-activity relationship of this chemotype was defined and culminated in the op…
View article: A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo
A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4
Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4 Open
The emergence of resistance against current antimalarial treatments has necessitated the need for the development of novel antimalarial chemotypes. Toward this goal, we recently optimised the antimalarial activity of the dihydroquinazolino…
View article: Property and Activity Refinement of Dihydroquinazolinone-3-carboxamides as Orally Efficacious Antimalarials that Target PfATP4
Property and Activity Refinement of Dihydroquinazolinone-3-carboxamides as Orally Efficacious Antimalarials that Target PfATP4 Open
To contribute to the global effort to develop new antimalarial therapies, we previously disclosed initial findings on the optimization of the dihydroquinazolinone-3-carboxamide class that targets PfATP4. Here we report on refining the aque…
View article: A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i>
A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i> Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: Mitochondrial ATP synthesis is essential for efficient gametogenesis in<i>Plasmodium falciparum</i>
Mitochondrial ATP synthesis is essential for efficient gametogenesis in<i>Plasmodium falciparum</i> Open
Interrupting parasite transmission from humans to mosquitoes is vital for malaria elimination and eradication. Plasmodium male and female gametocytes are the gatekeepers of human to mosquito transmission. Whilst dormant in the human host, …
View article: Optimisation-based modelling for explainable lead discovery in malaria
Optimisation-based modelling for explainable lead discovery in malaria Open
Three compounds are identified as potential leads for antimalarials using the methodology described above. This work illustrates how explainable predictive models based on mathematical optimisation can pave the way towards more efficient f…
View article: Aryl amino acetamides prevent the development of<i>Plasmodium falciparum</i>rings via inhibition of the lipid transfer protein PfSTART1
Aryl amino acetamides prevent the development of<i>Plasmodium falciparum</i>rings via inhibition of the lipid transfer protein PfSTART1 Open
With resistance to most antimalarials increasing, it is imperative that new antimalarial drugs are developed to replace or complement front-line artemisinin therapies. We previously identified an aryl acetamide compound, MMV006833 (M-833),…
View article: Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials
Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials Open
Preventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priorit…
View article: Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose
Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose Open
We designed and synthesized a series of symmetric bis-6-amidino-benzothiazole derivatives with aliphatic central units and evaluated their efficacy against bloodstream forms of the African trypanosome Trypanosoma brucei. Of these, a dicati…
View article: A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking in <i>Plasmodium falciparum</i> through Potential Inhibition of the Parasite’s PI4KIIIB Enzyme
A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking in <i>Plasmodium falciparum</i> through Potential Inhibition of the Parasite’s PI4KIIIB Enzyme Open
With the resistance increasing to current antimalarial medicines, there is an urgent need to discover new drug targets and to develop new medicines against these targets. We therefore screened the Open Global Health Library of Merck KGaA, …
View article: Machine Learning-based Phenotypic Imaging to Characterise the Targetable Biology of<i>Plasmodium falciparum</i>Male Gametocytes for the Development of Transmission-Blocking Antimalarials
Machine Learning-based Phenotypic Imaging to Characterise the Targetable Biology of<i>Plasmodium falciparum</i>Male Gametocytes for the Development of Transmission-Blocking Antimalarials Open
Preventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priorit…
View article: A novel class of sulphonamides potently block malaria transmission by targeting a <i>Plasmodium</i> vacuole membrane protein
A novel class of sulphonamides potently block malaria transmission by targeting a <i>Plasmodium</i> vacuole membrane protein Open
Phenotypic cell-based screens are critical tools for discovering candidate drugs for development, yet identification of the cellular target and mode of action of a candidate drug is often lacking. Using an imaging-based screen, we recently…
View article: The Novel bis-1,2,4-Triazine MIPS-0004373 Demonstrates Rapid and Potent Activity against All Blood Stages of the Malaria Parasite
The Novel bis-1,2,4-Triazine MIPS-0004373 Demonstrates Rapid and Potent Activity against All Blood Stages of the Malaria Parasite Open
Novel bis-1,2,4-triazine compounds with potent in vitro activity against Plasmodium falciparum parasites were recently identified. The bis-1,2,4-triazines represent a unique antimalarial pharmacophore and are proposed to act by a novel but…
View article: <i>Plasmodium falciparum</i> protein Pfs16 is a target for transmission-blocking antimalarial drug development
<i>Plasmodium falciparum</i> protein Pfs16 is a target for transmission-blocking antimalarial drug development Open
Phenotypic cell-based screens are critical to the discovery of new antimalarial lead compounds. However, identification and validation of cellular targets of lead compounds is required following discovery in a phenotypic screen. We recentl…
View article: Malaria Parasite Detection Using Deep Learning Methods
Malaria Parasite Detection Using Deep Learning Methods Open
Malaria is a serious disease which affects hundreds of millions of people around the world, each year. If not treated in time, it can be fatal. Despite recent developments in malaria diagnostics, the microscopy method to detect malaria rem…
View article: Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite <i>Plasmodium falciparum</i> and Optimization Efforts
Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite <i>Plasmodium falciparum</i> and Optimization Efforts Open
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich…