The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

• Klíčová slova
• biological chemistry, biomaterials, biomolecules, chemical biology, molecular interactions, natural compounds, proteins and nucleic acids, structure and dynamics, targeting, virtual screening,
• MeSH
• molekulární biologie * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as MYCN amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in MYCN-amplified and c-MYC in MYCN-nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.

• Klíčová slova
• DpC, EGFR, MYC, NDRG1, lipid droplet, neuroblastoma, thiosemicarbazone,
• MeSH
• amplifikace genu účinky léků   MeSH
• biologické modely MeSH
• chelátory železa farmakologie   MeSH
• down regulace účinky léků   MeSH
• erbB receptory metabolismus   MeSH
• fosforylace účinky léků   MeSH
• fyziologický stres účinky léků   MeSH
• intracelulární signální peptidy a proteiny metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• neuroblastom metabolismus   patologie   MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• protoonkogen n-myc metabolismus   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• pyridiny farmakologie   MeSH
• signální transdukce * MeSH
• thiosemikarbazony farmakologie   MeSH
• tvar buňky účinky léků   MeSH
• umlčování genů účinky léků   MeSH
• upregulace účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chelátory železa MeSH
• di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone MeSH Prohlížeč
• erbB receptory MeSH
• intracelulární signální peptidy a proteiny MeSH
• N-myc downstream-regulated gene 1 protein MeSH Prohlížeč
• proteiny buněčného cyklu MeSH
• protoonkogen n-myc MeSH
• protoonkogenní proteiny c-akt MeSH
• pyridiny MeSH
• thiosemikarbazony MeSH

A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action.

• MeSH
• antitumorózní látky chemická syntéza   chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• DNA metabolismus   MeSH
• doxorubicin farmakologie   MeSH
• HCT116 buňky MeSH
• interkalátory farmakologie   MeSH
• knihovny malých molekul chemie   farmakologie   MeSH
• lidé MeSH
• molekulární modely MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• naftoly chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• racionální návrh léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-naphthol MeSH Prohlížeč
• antitumorózní látky MeSH
• calf thymus DNA MeSH Prohlížeč
• DNA MeSH
• doxorubicin MeSH
• interkalátory MeSH
• knihovny malých molekul MeSH
• nádorový supresorový protein p53 MeSH
• naftoly MeSH

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.

• Klíčová slova
• chemical biology, drug design and development, medicinal chemistry, natural compounds, new small entities, organic synthesis, pharmaceutical analysis, therapeutic proteins,
• MeSH
• chemie farmaceutická MeSH
• farmaceuti MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• lidé MeSH
• mezisektorová spolupráce MeSH
• příprava léků * MeSH
• výzkumní pracovníci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kongresy MeSH
• Geografické názvy
• Slovenská republika MeSH