The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5-8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, Drug Synthesis and Analysis, meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting

Derivatives of Pyrazinecarboxylic Acid as Potential Antituberculotics (Synthesis and Biological Evaluation)

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Dpt. of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Jan Zitko Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of Doctoral Thesis: Derivatives of pyrazinecarboxylic acid as potential antituberculotics (synthesis and biological evaluation) This thesis deals with derivatives of pyrazine-2-carboxylic (POA) acid with potential antimycobacterial activity. In the theoretical part of the thesis there is a short description of tuberculosis (TB) disease, discussion of its epidemiology an associated risk factors of increasing resistance to fist-line antituberculars and the co-infection with HIV. Antituberculars used in clinical practice are described as well as the summary of new antituberculars under clinical trials is presented. Pyrazinamide (PZA) as one of the most important first-line antituberculars is in the focus of this thesis. Multiple up-to-date theories of PZA (POA) mechanism of action are described and discussed. Importantly, a summary of structural changes of PZA/POA attempted in the past to prepare new antituberculars is presented and the importance and relevance of individual structural changes is discussed. In the practical part of this thesis, 76 derivatives of PZA/POA were prepared, 68 of..

Intracellular trafficking of an anti - Amyloid Protein Precursor antibody.

Intracellular trafficking of an anti-Amyloid Protein Precursor antibody Alzheimer's disease is characterized by over-accumulation of beta-amyloid peptide (Aβ) in the brain. Aβ is produced by proteolytic cleavage of beta-amyloid precursor protein (APP) by β- and γ-secretases. Novel monoclonal antibody, 2B12, has been shown to bind to β-secretase cleavage site of APP, reducing the production of APP, presumably by preventing the cleavage by steric hindrance. 2B12 is hypothesized to bind to APP molecules exposed on the cell surface and to be internalized in the form of complex with APP via natural endocytic pathway. This hypothesis was confirmed by San Pei Ho's (2007), who followed the internalization of 2B12 in living astrocytoma MOG-G-UVW, cells in time-course experiment. This project is focused on intracellular trafficking of 2B12 and its localization within specific cellular compartments. Experiments were performed with fixed astrocytoma MOG- G-UVW cells (constitutively expressing APP). Originally planned experiments with live cells could not be performed due to decreased stability of 2B12 (causes remain unknown). 2B12 was tested for colocalization with polyclonal affinity purified antibodies labelling subcellular markers (proteins) associated with compartments known to participate in APP..

Sledování pohybu protilátky proti prekurzoru amyloidního proteinu v buňce

Intracelulární sledování pohybu protilátky proti amyloidnímu prekurzorovému proteinu Alzheimerova choroba je neuropatologické onemocnění, klinicky se projevující postupným zhoršováním funkcí centrální nervové soustavy, především pak paměti, kognitivních funkcí, změněným chováním (včetně paranoii) a zhoršováním jazykových funkcí. Alzheimerova choroba je nejčastější příčinou demence ve středním a vyšším věku. Příčiny a samotný proces rozvoje choroby nejsou doposud plně objasněny, nicméně jedním z rozhodujících faktorů se zdá být nahromadění β-amyloidního peptidu (Aβ) v určitých oblastech CNS. Aβ je ovšem přirozeným a fyziologickým metabolitem a lze ho izolovat z tělesných tekutin zdravých jedinců. Aβ vzniká proteolytickým štěpením amyloidního prekurzorového proteinu (APP), což je fyziologický, evolučně vysoce konzervativní, membránový protein. APP může být štěpen v takzvané neamyloidogenní cestě α-sekretázou a následně γ-sekretázou za vzniku dobře rozpustných peptidů nepodílejících se na vzniků depozitů, nebo β-sekretázou a γ-sekretázou za vzniku Aβ s tendencí k agregaci (amyloidogenní cesta). Pohyb APP v buňce je velmi komplexní. Po jeho syntéze je posttranslačně modifikován a distribuován sekreční cestou k buněčnému povrchu, kde je exponován. Poměrně rychle je APP podroben endocytóze a následně...Intracellular trafficking of an anti-Amyloid Protein Precursor antibody Alzheimer's disease is characterized by over-accumulation of beta-amyloid peptide (Aβ) in the brain. Aβ is produced by proteolytic cleavage of beta-amyloid precursor protein (APP) by β- and γ-secretases. Novel monoclonal antibody, 2B12, has been shown to bind to β-secretase cleavage site of APP, reducing the production of APP, presumably by preventing the cleavage by steric hindrance. 2B12 is hypothesized to bind to APP molecules exposed on the cell surface and to be internalized in the form of complex with APP via natural endocytic pathway. This hypothesis was confirmed by San Pei Ho's (2007), who followed the internalization of 2B12 in living astrocytoma MOG-G-UVW, cells in time-course experiment. This project is focused on intracellular trafficking of 2B12 and its localization within specific cellular compartments. Experiments were performed with fixed astrocytoma MOG- G-UVW cells (constitutively expressing APP). Originally planned experiments with live cells could not be performed due to decreased stability of 2B12 (causes remain unknown). 2B12 was tested for colocalization with polyclonal affinity purified antibodies labelling subcellular markers (proteins) associated with compartments known to participate in APP...Katedra farmaceutické chemie a kontroly léčivDepartment of Pharmaceutical Chemistry and Drug ControlFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov