Publications associées à Exploring the Versatility of Cycloplatinated Thiosemicarbazones as Antitumor and Antiparasitic Agents

Potent Virustatic Polymer-Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanopartides that mimic functional components of ...

AMER CHEMICAL SOC2022

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Vassily Hatzimanikatis, Noushin Hadadi, Jasmin Maria Hafner, Anush Chiappino-Pepe, Homa Mohammadi Peyhani

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

2021

Optimization methods and objective functions for analysis of metabolic network models

Zhaleh Hosseini

Computational studies of metabolism aim to systematically analyze the metabolic behaviour of biological systems in different conditions. Genome-scale metabolic network models (GEMs) capture the connection between elements of the network by applying stoichi ...

EPFL2020

Targeting liver stage malaria with metformin

Leonardo Filipe Lemos Rocha

Despite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise ...

2019

Analysis of cellular and drug action mechanisms in the malaria parasites using systems biology approaches

Anush Chiappino-Pepe

Malaria puts at risk of infection half of the world population and still kills around half a million people every year. The rapid and worrisome rise of drug-resistant malaria parasites hinders the treatment of malaria and calls for a global collaboration t ...

EPFL2018

Recent Advances of Malaria Parasites Detection Systems Based on Mathematical Morphology

Michel Kocher

Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis. Nevertheless, this kind of visual inspection is subjective, err ...

2018

Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks

Vassily Hatzimanikatis, Stepan Tymoshenko, Dominique Soldati-Favre, Meriç Ataman, Anush Chiappino-Pepe

Novel antimalarial therapies are urgently needed for the fight against drug-resistant para- sites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this co ...

Public Library of Science2017

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles

Luc Patiny, Eileen Ryan, Anna Lee

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explor ...

2016

Inhibition of the SR Protein-Phosphorylating CLK Kinases of Plasmodium falciparum Impairs Blood Stage Replication and Malaria Transmission

Cyclin-dependent kinase-like kinases (CLKs) are dual specificity protein kinases that phosphorylate Serine/Arginine-rich (SR) proteins involved in pre-mRNA processing. Four CLKs, termed PfCLK-1-4, can be identified in the human malaria parasite Plasmodium ...

Public Library Science2014

Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and Ir(III) pyridyl ester complexes as in vitro antiparasitic and antitumor agents

Paul Joseph Dyson, Tina Riedel

New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di- and tripyridyl ester ligands have been synthesised and characterised using analytical and spectroscopic techniques including H-1, C-13 NMR and infrared spectroscopy. Reactio ...

2014

Regulation of Plasmodium falciparum Development by Calcium-dependent Protein Kinase 7 (PfCDPK7)

Second messengers such as phosphoinositides and calcium are known to control diverse processes involved in the development of malaria parasites. However, the underlying molecular mechanisms and pathways need to be unraveled, which may be achieved by unders ...

Amer Soc Biochemistry Molecular Biology Inc2014

Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

Stewart Cole, Benoit Lechartier, Wei Zhu, Kai Li

We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), wh ...

Amer Chemical Soc2014

Functional genomics of Plasmodium falciparum using metabolic modelling and analysis

Rebecca Oppenheim, Vassily Hatzimanikatis, Stepan Tymoshenko, Dominique Soldati-Favre

Plasmodium falciparum is an obligate intracellular parasite and the leading cause of severe malaria responsible for tremendous morbidity and mortality particularly in sub-Saharan Africa. Successful completion of the P. falciparum genome sequencing project ...

Oxford Univ Press2013

Expression in Yeast Links Field Polymorphisms in PfATP6 to in Vitro Artemisinin Resistance and Identifies New Inhibitor Classes

Serena Pulcini

Background. The mechanism of action of artemisinins against malaria is unclear, despite their widespread use in combination therapies and the emergence of resistance. Results. Here, we report expression of PfATP6 (a SERCA pump) in yeast and demonstrate its ...

Oxford University Press2013

The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation

Miguel Garcia

Background: Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset ...

Biomed Central Ltd2012

Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway

Guillem Dayer, Marc Moniatte, Amit Sharma, Romain Hamelin

Background: Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of Plasmodium falciparum CK2 (PfCK2) are unknown. Th ...

2012

Toward Understanding the Chloroquine Action at the Molecular Level in Antimalarial Therapy - X-ray Absorption Studies in Acetic Add Solution

Andrzej Sienkiewicz

The local atomic structure around the central iron of the synthetic soluble analog of malarial pigment in acetic acid solution and with addition of chloroquine as found by X-ray absorption spectroscopy is reported. The special interest was drawn to the axi ...

2011

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

Yvan Bouza Lamigueiro, Claudia Demarta, Michele Graciotti

The role of protein phosphorylation in the life cycle of malaria parasites is slowly emerging. Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to assess the importance of protein phosphorylation in Plasmodium falciparum ...

Nature Research2011

Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes

Marc Moniatte, Romain Hamelin

P>Merozoites of malaria parasites invade red blood cells (RBCs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for malaria pathogenesis. Here, we report that a protein kinase-me ...

Wiley-Blackwell2011

Two Nucleus-Localized CDK-Like Kinases With Crucial Roles for Malaria Parasite Erythrocytic Replication Are Involved in Phosphorylation of Splicing Factor

The kinome of the human malaria parasite Plasmodium falciparum comprises representatives of most eukaryotic protein kinase groups, including kinases which regulate proliferation and differentiation processes. Despite extensive research on most plasmodial e ...

Wiley-Blackwell2011