The 5-aminolevulinic acid (5-ALA) prodrug is widely used in clinical applications, primarily for skin cancer treatments and to visualize brain tumors in neurosurgery. Unfortunately, its applications are limited by unfavorable pharmacological properties, especially low lipophilicity; therefore, efficient nanovehicles are needed. For this purpose, we synthesized and characterized two novel water-soluble fullerene nanomaterials containing 5-ALA and d-glucuronic acid components. Their physicochemical properties were investigated using NMR, XPS, ESI mass spectrometry, as well as TEM and SEM techniques. In addition, HPLC and fluorescence measurements were performed to evaluate the biological activity of the fullerene nanomaterials in 5-ALA delivery and photodynamic therapy (PDT); additional detection of selected mRNA targets was carried out using the qRT-PCR methodology. The cellular response to the [60]fullerene conjugates resulted in increased levels of ABCG2 and PEPT-1 genes, as determined by qRT-PCR analysis. Therefore, we designed a combination PDT approach based on two fullerene materials, C60-ALA and C60-ALA-GA, along with the ABCG2 inhibitor Ko143.

• Publikační typ
• časopisecké články 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
• 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
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• racionální návrh léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-naphthol MeSH Prohlížeč
• calf thymus DNA MeSH Prohlížeč
• DNA MeSH
• doxorubicin MeSH
• interkalátory MeSH
• knihovny malých molekul MeSH
• nádorový supresorový protein p53 MeSH
• naftoly MeSH
• protinádorové látky 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
• farmaceuti MeSH
• farmaceutická chemie 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

Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized "soft" donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.

• MeSH
• biologický transport účinky léků   MeSH
• kyselina askorbová metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• oxidace-redukce účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• racionální návrh léčiv * MeSH
• thiosemikarbazony chemická syntéza   chemie   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyselina askorbová MeSH
• protinádorové látky MeSH
• thiosemikarbazony MeSH
• železo MeSH