Université de Fribourg

Mechanism of cystathionine-β-synthase inhibition by disulfiram : The role of bis(N,N-diethyldithiocarbamate)-copper(II)

Zuhra, Karim ; Panagaki, Theodora ; B.Randi, Elisa ; Augsburger, Fiona ; Blondel, Marc ; Friocourt, Gaelle ; Herault, Yann ; Szabo, Csaba

In: Biochemical Pharmacology, 2020, vol. 182, p. 114267

Background: Hydrogen sulfide (H2S) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3- mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase and a clinically used drug in the treatment of...

Université de Fribourg

Screening of heteroaromatic scaffolds against cystathionine beta-synthase enables identification of substituted pyrazolo[3,4-c]pyridines as potent and selective orthosteric inhibitors

Fantel, Anna-Maria ; Myrianthopoulos, Vassilios ; Georgoulis, Anastasios ; Lougiakis, Nikolaos ; Zantza, Iliana ; Lamprinidis, George ; Augsburger, Fiona ; Marakos, Panagiotis ; Vorgias, Constantinos E. ; Szabo, Csaba ; Pouli, Nicole ; Papapetropoulos, Andreas ; Mikros, Emmanuel

In: Molecules, 2020, vol. 25, no. 16, p. 3739

Cystathionine β-synthase (CBS) is a key enzyme in the production of the signaling molecule hydrogen sulfide, deregulation of which is known to contribute to a range of serious pathological states. Involvement of hydrogen sulfide in pathways of paramount importance for cellular homeostasis renders CBS a promising drug target. An in-house focused library of heteroaromatic compounds was...

Université de Fribourg

Cystathionine-β-synthase: molecular regulation and pharmacological inhibition

Zuhra, Karim ; Augsburger, Fiona ; Majtan, Tomas ; Szabo, Csaba

In: Biomolecules, 2020, vol. 10, no. 5, p. 697

Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in the transsulfuration pathway, is an important mammalian enzyme in health and disease. Its biochemical functions under physiological conditions include the metabolism of homocysteine (a cytotoxic molecule and cardiovascular risk factor) and the generation of hydrogen sulfide (H2S), a gaseous biological mediator with...

Université de Fribourg

Role of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation, migration, and bioenergetics in murine colon cancer cells

Augsburger, Fiona ; Randi, Elisa B. ; Jendly, Mathieu ; Ascencao, Kelly ; Nahzli Dilek ; Szabo, Csaba

In: Biomolecules, 2020, vol. 10, no. 3, p. 447

3-mercaptopyruvate sulfurtransferase (3-MST) has emerged as one of the significant sources of biologically active sulfur species in various mammalian cells. The current study was designed to investigate the functional role of 3- MST’s catalytic activity in the murine colon cancer cell line CT26. The novel pharmacological 3-MST inhibitor HMPSNE was used to assess cancer cell proliferation,...

Université de Fribourg

Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells

Augsburger, Fiona ; Szabo, Csaba

In: Pharmacological Research, 2020, vol. 154, p. 104083

Hydrogen sulfide (H2S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2S biology, showing that various cancer cells upregulate their endogenous H2S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation,...

Université de Fribourg

Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome

Panagaki, Theodora ; Randi, Elisa B. ; Augsburger, Fiona ; Szabo, Csaba

In: Proceedings of the National Academy of Sciences, 2019, p. 201911895

Down syndrome (DS) is associated with significant perturbances in mitochondrial function. Here we tested the hypothesis that the suppression of mitochondrial electron transport in DS cells is due to high expression of cystathionine-β-synthase (CBS) and subsequent overproduction of the gaseous transmitter hydrogen sulfide (H2S). Fibroblasts from DS individuals showed higher CBS expression...