OBJECTIVES: Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule. METHODS: The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated. KEY FINDINGS: A series of 6-oxopyrano[3,4-c]pyridines 3a-j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well. CONCLUSIONS: Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail.
OBJECTIVES: The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine-induced chronic kidney disease (CKD) model. METHODS: Rats were orally given, for 28 consecutive days, either adenine alone or together with either aqueous extract of H. sabdariffa calyces (5 and 10%) or anthocyanins (50, 100 and 200 mg/kg of anthocyanin concentrate). For comparative purposes, two groups of rats were given lisinopril (10 mg/kg). KEY FINDINGS: When either H. sabdariffa aqueous extract or the anthocyanins isolated from it was administered along with adenine, the adverse effects of adenine-induced CKD were significantly lessened, mostly in a dose-dependent manner. The positive effects were similar to those obtained by administration of lisinopril. CONCLUSIONS: The results obtained show that both H. sabdariffa and its anthocyanins could be considered as possible promising safe dietary agents that could be used to attenuate the progression of human CKD. This could have added significance as H. sabdariffa tea is widely consumed in many parts of Africa and Asia and is thus readily available.
- MeSH
- adenin toxicita MeSH
- anthokyaniny aplikace a dávkování izolace a purifikace farmakologie MeSH
- aplikace orální MeSH
- chronická renální insuficience farmakoterapie patofyziologie MeSH
- Hibiscus chemie MeSH
- krysa rodu rattus MeSH
- lisinopril farmakologie MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- rostlinné extrakty aplikace a dávkování farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
OBJECTIVES: Flubendazole (FLU), a member of benzimidazole family of anthelmintic drugs, is able to inhibit proliferation of various cancer cells. The aim of present study was to elucidate the mechanisms of antiproliferative effect of FLU on colorectal cancer cells in vitro. METHODS: The effect of FLU on proliferation, microtubular network, DNA content, caspase activation and senescence induction was studied in SW480 and SW620 cell lines. KEY FINDINGS: Flubendazole significantly affected cell proliferation in a pattern typical for mitotic inhibitor. This was accompanied by decrease in cyclin D1 levels, increase in cyclin B1 levels, activation of caspase 2 and caspase 3/7 and PARP cleavage. Morphological observations revealed disruption of microtubular network, irregular mitotic spindles, formation of giant multinucleated cells and increase in nuclear area and DNA content. In SW620 cell line, 37.5% giant multinucleated cells induced by FLU treatment showed positivity for SA-β-galactosidase staining. Cell lines were able to recover from the treatment and this process was faster in SW480 cells. CONCLUSION: Flubendazole in low concentration temporarily inhibits cell proliferation and induces mitotic catastrophe and premature senescence in human colon cancer cells in vitro.
- MeSH
- aparát dělícího vřeténka účinky léků ultrastruktura MeSH
- lidé MeSH
- mebendazol analogy a deriváty farmakologie MeSH
- mikrotubuly účinky léků ultrastruktura MeSH
- mitóza účinky léků MeSH
- nádorové buněčné linie MeSH
- obrovské buňky účinky léků ultrastruktura MeSH
- proliferace buněk účinky léků MeSH
- stárnutí buněk účinky léků MeSH
- tubulin metabolismus MeSH
- velikost buněčného jádra účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Tenofovir and emtricitabine are very effective and well-tolerated antiretrovirals representing current backbone of the antiretroviral combination regimens for the prevention of perinatal HIV transmission. The aim of our study was to determine whether tenofovir or emtricitabine administered in long-term fashion affect expression of two widely described pharmacokinetic determinants, P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), in maternal or fetal biological tissues. METHODS: For this purpose, pregnant Wistar rats were administered tenofovir (2.25 mg/kg/day), emtricitabine (3.5 mg/kg/day) or saline i.m. for 10 days (from the 12th to 21st gestation day). On the 22nd day, the placenta and maternal/fetal intestine, brain, kidneys and liver were sampled and analysed for Abcb1a, Abcb1b and Abcg2 expression; placental and newborns' weights were also monitored. KEY FINDINGS: We found that long-term application of tenofovir or emtricitabine did not significantly affect expression of Abcb1a, Abcb1b and Abcg2 in either maternal or fetal organs. However, tenofovir administration significantly increased placenta-to-birthweight ratio, a strong indicator of various diseases occurring later in life. CONCLUSIONS: Our data broaden current knowledge on safety profile of tenofovir and emtricitabine use in pregnancy. Nevertheless, further research in other mammal species, including humans, is important to fully elucidate this issue.
- MeSH
- ABC transportéry metabolismus MeSH
- emtricitabin aplikace a dávkování MeSH
- krysa rodu rattus MeSH
- P-glykoproteiny metabolismus MeSH
- placenta účinky léků metabolismus MeSH
- plod účinky léků metabolismus MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- tenofovir aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: In this review, we highlight and summarise the most promising extracts, fractions and pure compounds as potential anti-herpes simplex virus (HSV) agents derived from microorganisms, marine organisms, fungi, animals and plants. The role of natural products in the development of anti-HSV drugs will be discussed. KEY FINDINGS: Herpes simplex viruses (HSV-1 and -2) are common human pathogens that remain a serious threat to human health. In recent years, a great interest has been devoted to the search for integrated management of HSV infections. Acyclovir and related nucleoside analogues have been licensed for the therapy that target viral DNA polymerase. Although these drugs are currently effective against HSV infections, the intensive use of these drugs has led to the problem of drug-resistant strains. Therefore, the search for new sources to develop new antiherpetic agents has gained major priority to overcome the problem. SUMMARY: Natural products as potential, new anti-HSV drugs provide several advantages such as reduced side effects, less resistance, low toxicity and various mechanisms of action. This paper aims to provide an overview of natural products that possess antiviral activity against HSV.
- MeSH
- antivirové látky škodlivé účinky izolace a purifikace farmakologie MeSH
- biologické přípravky škodlivé účinky izolace a purifikace farmakologie MeSH
- herpes simplex farmakoterapie virologie MeSH
- lidé MeSH
- lidský herpesvirus 1 izolace a purifikace MeSH
- racionální návrh léčiv MeSH
- virová léková rezistence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- arterioskleróza farmakoterapie MeSH
- cévní endotel účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- králíci MeSH
- lipoproteiny krev účinky léků MeSH
- molekuly buněčné adheze účinky léků MeSH
- simvastatin farmakologie terapeutické užití MeSH
- synthasa oxidu dusnatého účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- anilidy farmakologie MeSH
- antagonisté androgenů farmakologie MeSH
- dospělí MeSH
- geny p53 účinky léků MeSH
- lidé MeSH
- nádory prostaty genetika MeSH
- regulace genové exprese účinky záření MeSH
- telomerasa metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- MeSH
- antitumorózní látky farmakologie MeSH
- DNA-topoisomerasy I MeSH
- DNA-topoisomerasy typu II MeSH
- ethanolaminy farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- inhibitory enzymů farmakologie MeSH
- inhibitory topoisomerasy I MeSH
- inhibitory topoisomerasy II MeSH
- isochinoliny farmakologie MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- MeSH
- anorektika farmakokinetika chemie MeSH
- biotransformace MeSH
- buněčné kultury MeSH
- cyklobutany farmakokinetika chemie MeSH
- finanční podpora výzkumu jako téma MeSH
- hepatocyty metabolismus MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu rattus MeSH
- NADP metabolismus MeSH
- potkani Wistar MeSH
- stereoizomerie MeSH
- techniky in vitro MeSH
- viabilita buněk účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- antagonisté leukotrienů farmakokinetika MeSH
- biotransformace fyziologie MeSH
- chinoliny farmakokinetika MeSH
- finanční podpora výzkumu jako téma MeSH
- hepatocyty enzymologie MeSH
- jaterní mikrozomy enzymologie MeSH
- krysa rodu rattus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
