Cancer is most frequently treated with antineoplastic agents (ANAs) that are hazardous to patients undergoing chemotherapy and the healthcare workers who handle ANAs in the course of their duties. All aspects related to hazardous oncological drugs illustrate that the monitoring of ANAs is essential to minimize the risks associated with these drugs. Among all analytical techniques used to test ANAs, electrochemistry holds an important position. This review, for the first time, comprehensively describes the progress done in electrochemistry of ANAs by means of a variety of bare or modified (bio)sensors over the last four decades (in the period of 1982-2021). Attention is paid not only to the development of electrochemical sensing protocols of ANAs in various biological, environmental, and pharmaceutical matrices but also to achievements of electrochemical techniques in the examination of the interactions of ANAs with deoxyribonucleic acid (DNA), carcinogenic cells, biomimetic membranes, peptides, and enzymes. Other aspects, including the enantiopurity studies, differentiation between single-stranded and double-stranded DNA without using any label or tag, studies on ANAs degradation, and their pharmacokinetics, by means of electrochemical techniques are also commented. Finally, concluding remarks that underline the existence of a significant niche for the basic electrochemical research that should be filled in the future are presented.
- Klíčová slova
- Anticancer drugs, drugs-DNA interactions, drugs-cancer cells interactions, electroanalysis, electrochemical (bio)sensors,
- MeSH
- biosenzitivní techniky metody MeSH
- DNA chemie analýza MeSH
- elektrochemické techniky * MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- protinádorové látky * analýza chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
- protinádorové látky * MeSH
The consumption of hazardous antineoplastic drugs (ADs) used in anticancer chemotherapies is steadily increasing representing thus risks to both human health and the environment. Hospitals may serve as a contamination source, and pharmacists preparing the antineoplastic drugs (ADs) as well as nurses administering chemotherapy and caring for oncology patients are among the healthcare professionals being highly exposed. Here, we present the results of systematic monitoring (2018-2020) of surface contamination by 13 ADs in the pharmacies and hospitals in the Czech Republic (CZ; large-scale monitoring, 20 workplaces) and Slovak Republic (SK; pilot study at 4 workplaces). The study evaluated contamination by three commonly monitored ADs, i.e., 5-fluorouracil (FU), cyclophosphamide (CP), and platinum (total Pt representing cis-, carbo-, and oxaliplatin) together with ten less explored ADs, i.e., gemcitabine (GEM), ifosfamide (IF), paclitaxel (PX), irinotecan (IRI), docetaxel (DOC), methotrexate (MET), etoposide (ETOP), capecitabine (CAP), imatinib (IMAT), and doxorubicin (DOX). Floors and desktop surfaces in hospitals (chemotherapy application rooms, nurse working areas) were found to be more contaminated, namely with CP and Pt, in both countries when compared to pharmacies. Comparison between the countries showed that hospital surfaces in SK are generally more contaminated (e.g., CP median was 20 times higher in SK), while some pharmacy areas in the CZ were more contamined in comparison with SK. The newly studied ADs were detected at lower concentrations in comparison to FU, CP, and Pt, but some markers (GEM, IF, PX, and IRI) were frequently observed, and adding these compounds to routine monitoring is recommended.
- Klíčová slova
- 5-fluorouracil, Antineoplastic drugs, Cyclophosphamide, Gemcitabine, Hospital pharmacy, Occupational exposure, Platinum derivatives, Surface contamination,
- MeSH
- cyklofosfamid analýza MeSH
- fluoruracil analýza MeSH
- ifosfamid analýza MeSH
- kontaminace zdravotnického vybavení MeSH
- lékárny * MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- nemocnice MeSH
- pilotní projekty MeSH
- pracovní expozice * analýza MeSH
- protinádorové látky * analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Názvy látek
- cyklofosfamid MeSH
- fluoruracil MeSH
- ifosfamid MeSH
- protinádorové látky * MeSH
The cytotoxic properties of zinc nanoparticles have been evaluated in vitro against several types of cancer. However, there is a lack of significant evidence of their activity in vivo, and a potential therapeutic application remains limited. Herein we report the effective inhibition of tumor growth by zinc nanoparticles in vivo, as the effect of the dietary intervention, after the chemical induction in a rodent model of breast cancer. Biopsy images indicated grade 1 tumors with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, a moderately differentiated grade 2 adenocarcinoma was identified. Moreover, after the supplementation with zinc nanoparticles, the levels of several metabolites associated with cancer metabolism, important to its survival, were found to have been altered. We also revealed that the biological activity of zinc in vivo depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.
- Klíčová slova
- breast cancer, metabolomic, zinc nanoparticles,
- MeSH
- adenokarcinom metabolismus patologie prevence a kontrola MeSH
- kovové nanočástice aplikace a dávkování analýza MeSH
- krysa rodu Rattus MeSH
- nádory prsu metabolismus patologie prevence a kontrola MeSH
- nanotechnologie MeSH
- oxid zinečnatý chemie MeSH
- potkani Sprague-Dawley MeSH
- potravní doplňky MeSH
- protinádorové látky aplikace a dávkování analýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxid zinečnatý MeSH
- protinádorové látky MeSH
Sobuzoxane (MST-16) is an approved anticancer agent, a pro-drug of bisdioxopiperazine analog ICRF-154. Due to the structural similarity of ICRF-154 to dexrazoxane (ICRF-187), MST-16 deserves attention as a cardioprotective drug. This study presents for the first time UHPLC-MS/MS assay of MST-16, ICRF-154 and its metabolite (EDTA-diamide) in cell culture medium, buffer, plasma and cardiac cells and provides data on MST-16 bioactivation under conditions relevant to investigation of cardioprotection of this drug. The analysis of these compounds that differ considerably in their lipophilicity was achieved on the Zorbax SB-Aq column using a mixture of aqueous ammonium formate and methanol as a mobile phase. The biological samples were either diluted or precipitated with methanol, which was followed by acidification for the assay of MST-16. The method was validated for determination of all compounds in the biological materials. The application of the method for analysis of samples from in vitro experiments provided important findings, namely, that (1) MST-16 is quickly decomposed in biological environments, (2) the cardiac cells actively metabolize MST-16, and (3) MST-16 readily penetrates into the cardiac cells and is converted into ICRF-154 and EDTA-diamide. These data are useful for the in-depth examination of the cardioprotective potential of this drug.
- MeSH
- EDTA chemie MeSH
- kardiomyocyty cytologie metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- piperaziny analýza MeSH
- potkani Wistar MeSH
- protinádorové látky analýza metabolismus MeSH
- razoxan analogy a deriváty chemie metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,2-bis(3,5-dioxopiperazin-1-yl)ethane MeSH Prohlížeč
- EDTA MeSH
- piperaziny MeSH
- protinádorové látky MeSH
- razoxan MeSH
- sobuzoxane MeSH Prohlížeč
N2-(4-Amino-cyclohexyl)-9-cyclopentyl-N6-(6-furan-2-yl-pyridine-3-ylmethyl)-9H-purine-2,6-diamine (BP-14) and 2-(5-{[2-(4-amino-cyclohexylamino)-9-cyclopentyl-9H-purine-6-ylamino]-methyl}-pyridine-2-yl)-phenol (BP-20) are novel cyclin-dependent kinase inhibitors, structurally related to roscovitine, with significant biological activity. A simple, selective and sensitive liquid chromatography - tandem mass spectrometry method for determining them in rat plasma, using roscovitine as an internal standard, was developed and validated. Chromatographic separation was performed in reversed phase mode on Acquity BEH C18 column (100 × 2.1 mm, 1.7 μm) by gradient elution with mobile phases composed of 15 mM ammonium formate pH 4.0 and methanol at flow rate 0.25 mL/min at 40 °C. The analytes were detected based on their characteristic multiple reaction monitoring transitions in positive electrospray ionization mode m/z 473.07 > 157.93 for BP-14, m/z 499.62 > 184.2 for BP-20 and m/z 355.5 > 90.86 for internal standard. In plasma the method provided good linearity within the entire concentration range: 1-10,000 nmol/L (r2 = 0.9989) for BP-14 and 10-25,000 nmol/L (r2 = 0.9994) for BP-20; the limit of detection was 0.6 nmol/L for BP-14 and 6.1 nmol/L for BP-20. Validation was also performed in bile and urine. The results of validation fit within the acceptance limits following European Medicines Agency guidelines. The method was applied in a pharmacokinetic study of BP-14 and BP-20 in vivo in rats following intravenous and intraduodenal administration including plasma pharmacokinetics, tissue distribution and excretion (renal and biliary). Both compounds showed low bioavailability after intraduodenal administration (0.630 and 1.58% for BP-14 and BP-20, respectively). Distribution into all the analyzed tissues (brain, lungs, liver, kidney, spleen, muscle, adipose tissue) was observed 3 h after single dose administration, the highest and lowest concentrations being reached in the adipose tissue and brain, respectively. The biliary excretion of the parent BP-14 and BP-20 compounds accounted for 4.81% and 10.6% of the doses, respectively, and renal excretion for <0.5% in both cases. The obtained results represent pilot knowledge for further development of a new generation of compounds with strong anticancer activities.
- Klíčová slova
- BP-14, BP-20, Cyclin-dependent kinase inhibitor, Pharmacokinetics, Tissue distribution,
- MeSH
- 2-aminopurin analogy a deriváty analýza farmakokinetika MeSH
- biologická dostupnost MeSH
- cykliny chemie MeSH
- hepatobiliární exkrece účinky léků MeSH
- inhibitory proteinkinas aplikace a dávkování analýza chemie farmakokinetika MeSH
- intravenózní podání metody MeSH
- kalibrace MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- limita detekce MeSH
- molekulární struktura MeSH
- potkani Wistar MeSH
- protinádorové látky aplikace a dávkování analýza chemie farmakokinetika MeSH
- reprodukovatelnost výsledků MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- tkáňová distribuce účinky léků MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2-aminopurin MeSH
- cykliny MeSH
- inhibitory proteinkinas MeSH
- N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-((6-(2-furyl)-3-pyridyl)methyl)purine-2,6-diamine MeSH Prohlížeč
- protinádorové látky MeSH
BACKGROUND: Lichens provide a large array of compounds with the potential for pharmaceutical development. In the present study, extracts from three previously undescribed North American lichen species were examined for antioxidant, antibacterial and anticancer activities. RESULTS: The results from this study demonstrated the following: (i) Acarospora socialis ethanol extract exhibited significant DPPH antioxidant scavenging activities, which were concentration dependent; (ii) acetone and ethyl acetate extracts of Xanthoparmelia mexicana inhibited Gram-positive bacteria but had no effect on Gram-negative bacteria; X. mexicana acetone extract yielded a minimum inhibitory concentration (MIC) of 20.9 µg mL-1 against Staphylococcus aureus, and 41.9 µg mL-1 against Enterococcus faecalis; (iii) acetone extract of Lobothallia alphoplaca inhibited growth of cultured breast cancer MCF-7 cells with an effective concentration (EC50 ) of 87 µg mL-1 ; the MCF-7 cell cycle appears arrested in the G2 phase, whereas the DNA synthesis cell cycle (S) may be inhibited. CONCLUSION: New lichen species that possess strong biological activities have been identified. These lichens comprise secondary metabolites that possess antioxidant, antibacterial and anticancer properties. © 2017 Society of Chemical Industry.
- Klíčová slova
- Acarospora socialis, Lobothallia alphoplaca, North America, Xanthoparmelia mexicana, biological activities, lichens,
- MeSH
- antibakteriální látky analýza farmakologie MeSH
- antioxidancia analýza farmakologie MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- lidé MeSH
- lišejníky chemie metabolismus MeSH
- MFC-7 buňky MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky analýza farmakologie MeSH
- rostlinné extrakty farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Severní Amerika MeSH
- Názvy látek
- antibakteriální látky MeSH
- antioxidancia MeSH
- protinádorové látky MeSH
- rostlinné extrakty MeSH
UNLABELLED: In the last few decades, Hibiscus sabdariffa L. (Malvaceae; H. sabdariffa) has gained much attention in research field because of its potentially useful bioactivity as well as a great safety and tolerability. For decades, microbial, parasitic and cancer diseases remain a serious threat to human health and animals as well. To treat such diseases, a search for new sources such as plants that provide various bioactive compounds useful in the treatment of several physiological conditions is urgently needed, since most of the drugs currently used in the therapy have several undesirable side effects, toxicity, and drug resistance. In this paper, we aim to present an updated overview of in vitro and in vivo studies that show the significant therapeutic properties of the crude extracts and phytochemicals derived from H. sabdariffa as antimicrobial, antiparasitic, and anticancer agents. The future directions of the use of H. sabdariffa in clinical trials will be discussed. KEY WORDS: Hibiscus sabdariffa L. antimicrobial agents cancer preventive agents antiparasitic drugs natural products.
- MeSH
- antiinfekční látky analýza terapeutické užití MeSH
- fytonutrienty analýza terapeutické užití MeSH
- fytoterapie MeSH
- Hibiscus * MeSH
- lidé MeSH
- protinádorové látky analýza terapeutické užití MeSH
- rostlinné extrakty analýza terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antiinfekční látky MeSH
- fytonutrienty MeSH
- protinádorové látky MeSH
- rostlinné extrakty MeSH
The results of an inter-laboratory comparison exercise to determine cytostatic anticancer drug residues in surface water, hospital wastewater and wastewater treatment plant effluent are reported. To obtain a critical number of participants, an invitation was sent out to potential laboratories identified to have the necessary knowledge and instrumentation. Nine laboratories worldwide confirmed their participation in the exercise. The compounds selected (based on the extent of use and laboratories capabilities) included cyclophosphamide, ifosfamide, 5-fluorouracil, gemcitabine, etoposide, methotrexate and cisplatinum. Samples of spiked waste (hospital and wastewater treatment plant effluent) and surface water, and additional non-spiked hospital wastewater, were prepared by the organising laboratory (Jožef Stefan Institute) and sent out to each participant partner for analysis. All analytical methods included solid phase extraction (SPE) and the use of surrogate/internal standards for quantification. Chemical analysis was performed using either liquid or gas chromatography mass (MS) or tandem mass (MS/MS) spectrometry. Cisplatinum was determined using inductively coupled plasma mass spectrometry (ICP-MS). A required minimum contribution of five laboratories meant that only cyclophosphamide, ifosfamide, methotrexate and etoposide could be included in the statistical evaluation. z-score and Q test revealed 3 and 4 outliers using classical and robust approach, respectively. The smallest absolute differences between the spiked values and the measured values were observed in the surface water matrix. The highest within-laboratory repeatability was observed for methotrexate in all three matrices (CV ≤ 12 %). Overall, inter-laboratory reproducibility was poor for all compounds and matrices (CV 27-143 %) with the only exception being methotrexate measured in the spiked hospital wastewater (CV = 8 %). Random and total errors were identified by means of Youden plots.
- Klíčová slova
- Cytostatic, Hospital effluent, Inter-laboratory study, Pharmaceutical, Surface water, Wastewater,
- MeSH
- chemické látky znečišťující vodu analýza MeSH
- chromatografie kapalinová metody MeSH
- monitorování životního prostředí metody MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- protinádorové látky analýza MeSH
- reprodukovatelnost výsledků MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- protinádorové látky MeSH
- MeSH
- benzamidy analýza MeSH
- imatinib mesylát MeSH
- lidé MeSH
- monitorování léčiv * MeSH
- piperaziny analýza MeSH
- protinádorové látky analýza MeSH
- pyrimidiny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzamidy MeSH
- imatinib mesylát MeSH
- piperaziny MeSH
- protinádorové látky MeSH
- pyrimidiny MeSH
Ferrocenes represent an interesting group of drugs with potential antitumor properties. Moreover, their electronic properties make them suitable for electrochemical studies. We determined an uptake of a novel ferrocene derivative in low μM concentrations by selected cancer cell lines and showed its localization predominantly in cytoplasm, using glassy carbon electrodes.
- MeSH
- elektrochemické techniky * MeSH
- elektrody MeSH
- lidé MeSH
- metaloceny MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- protinádorové látky analýza farmakologie MeSH
- reaktivní formy kyslíku chemie MeSH
- viabilita buněk účinky léků MeSH
- železnaté sloučeniny chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ferrocene MeSH Prohlížeč
- metaloceny MeSH
- protinádorové látky MeSH
- reaktivní formy kyslíku MeSH
- železnaté sloučeniny MeSH