Publications associées à CZE-ICP-MS as a tool for studying the hydrolysis of ruthenium anticancer drug candidates and their reactivity towards the DNA model compound dGMP

Computational characterisation of the selectivity and binding mode of mono- and binuclear transition metal based anticancer compounds

The rising resistance and the severe side effects associated with classical anticancer drugs such as cisplatin or mercaptopurines has triggered the development of novel antitumourous agents based on transition metal (e.g. ruthenium, osmium, and gold) organ ...

EPFL2020

The mechanism of tumour cell death by metal-based anticancer drugs is not only a matter of DNA interactions

Paul Joseph Dyson, Gianni Sava

Platinum drugs are extensively used in the clinic to treat cancer, often leading to a palliative response rather than a cure. While DNA is considered to be the primary target of platinum drugs, there is no clear relationship between cellular platinum accum ...

2018

Development of mass spectrometric methods to understand the mechanism of action of transition metal-based anticancer compounds

Fook Seng Ronald Lee

Metal based anti-cancer drugs (metallodrugs) such as cisplatin are a cornerstone of cancer chemotherapy. However, development of this class of compound has been hindered by our lack of understanding of how they function. This is mainly because existing met ...

EPFL2016

Protein ruthenation and DNA alkylation: chlorambucil-functionalized RAPTA complexes and their anticancer activity

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Olivier Pierre Zava

Chemotherapeutics for the treatment of tumorigenic conditions that feature novel modes of action are highly sought after to overcome the limitations of current chemotherapies. Herein, we report the conjugation of the alkylating agent chlorambucil to the RA ...

2015

Crystallization of undercooled liquid fenofibrate

Esther Amstad

Formulation of hydrophobic drugs as amorphous materials is highly advantageous as this increases their solubility in water and therefore their bioavailability. However, many drugs have a high propensity to crystallize during production and storage, limitin ...

Royal Society of Chemistry2015

In vivo anti-tumor activity of the organometallic ruthenium(II)-arene complex [Ru(eta(6)-p-cymene)-Cl-2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

Paul Joseph Dyson, Maxime Dubois, Patrycja Nowak-Sliwinska

Based on the clinical success of platinum-based anti-cancer drugs such as cisplatin, carboplatin and oxaliplatin, a variety of other metal-based anti-cancer compounds are being investigated. In particular, a number of ruthenium-based compounds have been id ...

2014

Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity

Paul Joseph Dyson, Ursula Röthlisberger, Wee Han Ang, Pablo Campomanes Ramos, Alexey Nazarov, Michael Groessl, Catherine Marie Amélie Clavel

Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly ...

Nature Research2014

Combining RNAi and in vivo confocal microscopy analysis of the photoconvertible fluorescent protein Dendra2 to study a DNA repair protein

Matteo Di Piazza

Clinical approaches for tumor treatment often rely on combination therapy where a DNA damaging agent is used in combination with a DNA repair protein inhibitor. For this reason, great efforts have been made during the last decade to identify inhibitors of ...

Biotechniques Office2013

Study of Topoisomerase-DNA Interaction Using Atomic Force Microscopy

Livan Bladimir Alonso Sarduy

The aim of this thesis was to explore the topoisomerase-DNA interactions using atomic force microscopy (AFM) in a liquid environment. Firstly, we present a programmable microcontroller-driven injection system for the exchange of an imaging medium while usi ...

EPFL2012

Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation

Paul Joseph Dyson, Alexey Nazarov

Heavy metal compounds have toxic and medicinal potential through capacity to form strong specific bonds with macromolecules, and the interaction of platinum drugs at the major groove nitrogen atom of guanine bases primarily underlies their therapeutic acti ...

Oxford University Press2011

Chemistry and Biology of Natural Products : Applications in Cancer and Infectious Diseases

Jean-Yves Wach

This thesis is divided in four independent parts related to four different research projects. Each chapter describes one of the multiple aspects covered by organic chemistry, such as the generation of functional interfaces, understanding of biological proc ...

EPFL2011

Molecular Mechanisms and Proposed Targets for Selected Anticancer Gold Compounds

Angela Casini

Nowadays, gold compounds constitute a family of very promising experimental agents for cancer treatment. Indeed, several gold(I) and gold(III) compounds were shown to manifest outstanding antiproliferative properties in vitro against selected human tumor c ...

2010

Organometallic antitumour agents with alternative modes of action

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Angela Casini

The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially aba ...

2010

Chemistry, antiproliferative properties, tumor selectivity, and molecular mechanisms of novel gold(III) compounds for cancer treatment: a systematic study

Angela Casini

The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell li ...

Springer-Verlag2009

Interferon alpha sequential regimen for treating cancers

The present invention relates to a method of treating cancers, especially those showing resistance to classical anti-pro liferative chemotherapy drugs. Further, the invention provides a specific interferon alpha sequential regimen for treating cancers, esp ...

2008

Gold(III) compounds as anticancer agents: Relevance of gold-protein interactions for their mechanism of action

Paul Joseph Dyson, Christian Hartinger, Angela Casini

Gold(III) compds. constitute an emerging class of biol. active substances, of special interest as potential anticancer agents. During the past decade a no. of structurally diverse gold(III) complexes were reported to be acceptably stable under physiol.-lik ...

2008

Structure-activity relationships for ruthenium(II)-arene drugs : in vitro and in vivo antitumour evaluation

Claudine Scolaro

The discovery of the anticancer properties of cisplatin in 1965 heralded the development of metallopharmaceuticals and founded a revolution in cancer therapy. Platinum drugs are believed to induce cytotoxicity by cross-linking DNA, causing changes to the D ...

EPFL2007

Novel strategies for overcoming drug resistance in transition metal-based anticancer compounds

Wee Han Ang

Cisplatin is one of the most important and widely used anticancer drug in clinical use. However, its effectiveness is limited by its high toxicity and incidence of drug resistance. This has provided motivation for the search for transition metal-based drug ...

EPFL2007

Binding of organoruthenium anticancer drugs to DNA

Ursula Röthlisberger, Ivano Tavernelli, Christian Gossens

Organoruthenium compds. have emerged as promising novel anticancer agents but very little is known about their mol. mechanism of action. Here, we present classical and mixed QM/MM first-principles MD simulations of two ruthenium(II) compds. and their bindi ...

2005