ORCID Profile
0000-0003-2436-7037
Current Organisation
Beckman Coulter LS
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Publisher: American Chemical Society (ACS)
Date: 17-07-2017
DOI: 10.1021/ACS.JMEDCHEM.7B00140
Abstract: Structural optimization of 3-hydroxy-N'-arylidenepropanehydrazonamides provided new analogs with nanomolar to subnanomolar antiplasmodial activity against asexual blood stages of Plasmodium falciparum, excellent parasite selectivity, and nanomolar activity against the earliest forms of gametocyte development. Particularly, derivatives with a 1,3-dihalo-6-trifluoromethylphenanthrene moiety showed outstanding in vivo properties and demonstrated in part curative activity in the Plasmodium berghei mouse model when administered perorally.
Publisher: Wiley
Date: 13-09-2017
Abstract: In this work we aimed to develop parasite-selective histone deacetylase inhibitors (HDAC) inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis, and biological testing of a series of 13 terephthalic acid-based HDAC inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC
Publisher: Springer Science and Business Media LLC
Date: 15-06-2016
DOI: 10.1038/NCOMMS11901
Abstract: Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a erse set of antimalarial compounds to investigate the acquisition of drug resistance and the degree of cross-resistance against common resistance alleles. We assess cross-resistance using a set of 15 parasite lines carrying resistance-conferring alleles in pfatp4 , cytochrome bc 1 , pfcarl , pfdhod, pfcrt , pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase or hsp90 . Subsequently, we assess whether resistant parasites can be obtained after several rounds of drug selection. Twenty-three of the 48 in vitro selections result in resistant parasites, with time to resistance onset ranging from 15 to 300 days. Our data indicate that pre-existing resistance may not be a major hurdle for novel-target antimalarial candidates, and focusing our attention on fast-killing compounds may result in a slower onset of clinical resistance.
Publisher: Rockefeller University Press
Date: 28-06-2010
DOI: 10.1084/JEM.20091975
Abstract: Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells.
Publisher: Elsevier BV
Date: 07-2014
Publisher: American Chemical Society (ACS)
Date: 14-09-2016
Publisher: American Chemical Society (ACS)
Date: 10-09-2016
Publisher: American Chemical Society (ACS)
Date: 17-06-2016
Publisher: American Chemical Society (ACS)
Date: 26-10-2016
DOI: 10.1021/ACS.JMEDCHEM.6B01265
Abstract: Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγ
Publisher: Springer Science and Business Media LLC
Date: 25-05-2016
DOI: 10.1038/NATURE18280
Publisher: Public Library of Science (PLoS)
Date: 28-07-2016
Publisher: Springer Science and Business Media LLC
Date: 27-11-2013
DOI: 10.1038/NATURE12782
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-12-2011
Abstract: Imidazolopiperazine compounds inhibit liver-stage malaria parasites with one oral dose in mice.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-12-2018
Abstract: Malaria parasites are evolutionarily prepared to resist drug attack. Resistance is emerging to even the latest frontline combination therapies, which target the blood stages of the Plasmodium parasite. As an alternative strategy, Antonova-Koch et al. investigated the possibilities of drugs against liver-stage parasites (see the Perspective by Phillips and Goldberg). To do so, they devised a luciferase-reporter drug screen for the rodent parasite Plasmodium berghei. Three rounds of increasingly stringent screening were used. From this regime, several chemotypes that inhibit Plasmodium mitochondrial electron transport were identified. Excitingly, several new scaffolds, with as-yet-unknown modes of action but solely targeting the parasites' liver stages, emerged as promising drug leads for further development. Science , this issue p. eaat9446 see also p. 1112
Publisher: Springer Science and Business Media LLC
Date: 17-06-2015
DOI: 10.1038/NATURE14451
No related grants have been discovered for Stephan Meister.