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Institute: Institute of Experimental Pharmacology & Toxicology

Evaluation of Quercetin and Green Tea in combination with Methotrexate for arthritis therapy (Acronym: PhytoArt 2.0)
Evaluation of Quercetin and Green Tea in combination with Methotrexate for arthritis therapy (Acronym: PhytoArt 2.0)
Program: Bilateral - other
Project leader: PharmDr. Bauerová Katarína PhD., DrSc.
Duration: 1.1.2016 - 31.12.2017

Targeting Molecular Pathways of Glucolipotoxicity by a Novel Carboxymethylated Mercaptotriazinoindole Inhibitor of Aldo-Keto Reductase AKR1B1 In Diabetes, Inflammation and Age-related Neurodegeneration
Ovplyvnenie molekulovych dráh glucolipotoxicity novým karboxymetylovaným merkaptotriazinoindolovým ihibítorom aldo-ketoreduktázy AKRlBl v diabete, zápale a vekom podmienenej neurodegeneráci
Program: Bilateral - other
Project leader: Ing. Štefek Milan CSc.
Annotation:Novel therapeutic strategies for attenuating glucolipotoxicity leading to development of chronic diabetic complications, inflammatory disorders and age-related neurodegeneration are urgently needed for diabetic population. Aldo-keto reductases have been implicated in pathophysiology of diabetic complications mainly via functioning of aldose reductase (ALR2, AKR1B1) in the polyol pathway. These enzymes are also known to reduce the lipid peroxidation-derived aldehydes, such as 4-hydroxy-trans-2-nonenal (HNE) and their glutathione conjugates (e.g. GS-HNE), to corresponding alcohols which mediate the inflammatory signals. In addition, diabetics are prone to accelerated neurodegeneration. The main scientific goal of the joint project comprises a multidisciplinary approach to the detailed characterization of functional effects of CMTI, a novel carboxymethylated mercapto-triazinoindole inhibitor of aldo-keto reductases, on multiple glucolipotoxicity pathways. The aim of the study will be reached through specific tasks including in silico modelling, studies under in vitro conditions at the level of isolated enzymes and cells, ex vivo studies on isolated rat eye lenses and sciatic nerves, and in vivo studies in models of STZ diabetic rats, ZDF rats and experimental colitis. We believe that with the projected experiments we will for the first time firmly establish whether CMTI has ability to interfere with molecular mechanisms of glycolipotoxicity and whether these effects are mediated by the inhibition of aldo-keto reductases. Therapeutic potential of CMTI is expected in relation to late diabetic complications, inflammatory disorders and age-related neurodegeneration. The results will contribute vitally to a preclinical evaluation of CMTI as a potential drug.
Duration: 1.5.2016 - 30.4.2019

Challenging organic synthesis inspired by nature - from natural products to drug discovery.
Podnetné organické syntézy inšpirované prírodou: od chémie prírodných látok poobjav liečiv
Program: COST
Project leader: RNDr. Horáková Ľubica PhD.
Annotation:Natural products (NP) have had a major impact on chemistry, chemical biology and drug discovery and have been part of medical remedies since ancient times. Nowadays, NP represent a unique source of leads for medicinal chemistry and drugs derived from NP have found widespread use for the treatment of cancer, cardiovascular diseases, bacterial and fungal infections. The general aim of this COST Action is to advance the field and to maintain the high level of expertise in NP chemistry within Europe by combining synthetic chemistry, computational chemistry, chemical biology, and pharmacology to find new lead structures of pharmaceutical relevance. Since chemistry plays a key role in addressing the industrial requirements for preclinical candidates in terms of physicochemical properties of NP and their analogues, this Action further aims to promote the translation between fundamental academic research and industrial drug discovery by means of NP chemistry.
Duration: 15.3.2015 - 14.3.2019

Multi-target paradigm for innovative ligand identification in the drug discovery process
Viac-cieľový model pre inovatívnu identifikáciu látok v procese objavovania liečiv
Program: COST
Project leader: RNDr. Májeková Magdaléna PhD.
Annotation:The aim of this COST Action is to join highly-qualified research teams working in disciplines around the field of medicinal chemistry, into a novel network devoted to the multi-target issue in drug discovery. The choice of this theme is related to its marked multidisciplinary character, which can ensure a strong interaction among all COST Action participants. Currently, an important and emerging issue in modern drug discovery is to design novel or identify existing bioactive compounds, endowed with the capability to interact selectively with two or more macromolecular targets, exerting their effects against certain therapeutic goals in a synergic fashion. This leading concept stimulated this COST Action focusing on novel ligands able to recognize selected multiple targets, to promote closer scientific links among European research groups involved in medicinal chemistry field at both academic and industrial level. The research competencies of the network will span around medicinal chemistry, from synthetic chemistry, natural products and biophysics to theoretical chemistry, molecular modelling and biological screening.
Duration: 4.12.2015 - 29.10.2019

The total number of projects: 4