Kadlecová, Alena* Dotaz Zobrazit nápovědu
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
It has been more than 60 years since the discovery of kinetin, the first known member of a group of plant hormones called cytokinins. In this review we summarize the health-promoting activity of kinetin in animal systems, ranging from cells cultured in vitro through invertebrates to mammals. Kinetin has been shown to modulate aging, to delay age-related physiological decline and to protect against some neurodegenerative diseases. We also review studies on its mechanism of action, as well as point out gaps in our current knowledge.
- MeSH
- cytokininy MeSH
- kinetin farmakologie terapeutické užití MeSH
- lidé MeSH
- stárnutí * MeSH
- zdravé stárnutí * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVES: This study aimed to characterise compounds with activity against carbapenemase-expressing Gram-negative bacteria and nematodes and evaluate their cytotoxicity to non-cancerous human cells. METHODS: The antimicrobial activity and toxicity of a series of phenyl-substituted urea derivatives were evaluated using broth microdilution, chitinase, and resazurin reduction assays. RESULTS: The effects of different substitutions present on the nitrogen atoms of the urea backbone were investigated. Several compounds were active against Staphylococcus aureus and Escherichia coli control strains. Specifically, derivatives 7b, 11b, and 67d exhibited antimicrobial activity against Klebsiella pneumoniae 16, a carbapenemase-producing Enterobacteriaceae species, with minimum inhibitory concentration (MIC) values of 100, 50, and 72 μM (32, 64, and 32 mg/L), respectively. In addition, the MICs obtained against a multidrug-resistant E. coli strain were 100, 50, and 36 μM (32, 16, and 16 mg/L) for the same compounds, respectively. Furthermore, the urea derivatives 18b, 29b, 50c, 51c, 52c, 55c-59c, and 62c were very active towards the nematode Caenorhabditis elegans. CONCLUSIONS: Testing on non-cancerous human cell lines suggested that some of the compounds have the potential to affect bacteria, especially helminths, with limited cytotoxicity to humans. Given the simplicity of synthesis for this class of compounds and their potency against Gram-negative, carbapenemase-expressing K. pneumoniae, aryl ureas possessing the 3,5-dichloro-phenyl group certainly warrant further investigation to exploit their selectivity.
Cytokinins are phytohormones that are involved in many processes in plants, including growth, differentiation and leaf senescence. However, they also have various activities in animals. For example, kinetin and trans-zeatin can reduce levels of several aging markers in human fibroblasts. Kinetin can also protect mice against oxidative and glyoxidative stress, and prolong fruit flies' lifespan. Additionally, several cytokinins are currently used in cosmetics. To extend knowledge of the breadth of cytokinins' activities, we examined effects of natural cytokinin bases on the model nematode Caenorhabditis elegans. We found that kinetin, para-topolin and meta-topolin prolonged the lifespan of C. elegans. Kinetin also protected the organism against oxidative and heat stress. Furthermore, our results suggest that presence of reactive oxygen species, but not DAF-16 (the main effector of the insulin/insulin-like growth factor signaling pathway), is required for the beneficial effects of kinetin. Ultra-high performance liquid chromatography-tandem mass spectrometric analysis showed that kinetin is unlikely to occur naturally in C. elegans, but the worm efficiently absorbs and metabolizes it into kinetin riboside and kinetin riboside-5'-monophosphate.
- MeSH
- Caenorhabditis elegans účinky léků genetika fyziologie MeSH
- cytokininy farmakokinetika farmakologie MeSH
- dlouhověkost účinky léků fyziologie MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- inzulin metabolismus MeSH
- kinetin farmakokinetika farmakologie MeSH
- mutace MeSH
- oxidační stres účinky léků MeSH
- proteiny Caenorhabditis elegans genetika metabolismus MeSH
- reakce na tepelný šok účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulátory růstu rostlin farmakokinetika farmakologie MeSH
- signální transdukce účinky léků MeSH
- termotolerance účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
A small library of 2-[(1H-indol-3-yl)methyl]-5-(alkylthio)-1,3,4-oxadiazoles was prepared, starting from indole-3-acetic acid methyl ester and its 5-methyl-substituted derivative. The synthetic route involved the formation of intermediate hydrazides, their condensation with carbon disulfide, and intramolecular cyclization to corresponding 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones. The latter were then S-alkylated, and in case of ester derivatives, they were further hydrolyzed into corresponding carboxylic acids. All 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their S-alkylated derivatives were then screened for their protective effects in vitro and in vivo. Methyl substitution on the indole ring and propyl, butyl, or benzyl substitution on sulfhydryl group-possessing compounds were revealed to protect Friedreich's ataxia fibroblasts against the effects of glutathione depletion induced by the γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine. Two of the active compounds also reproducibly increased the survival of Caenorhabditis elegans exposed to juglone-induced oxidative stress.
- MeSH
- acetáty chemická syntéza MeSH
- antioxidancia * chemická syntéza chemie farmakologie MeSH
- Caenorhabditis elegans MeSH
- Friedreichova ataxie farmakoterapie metabolismus patologie MeSH
- indoly * chemie farmakologie MeSH
- kultivované buňky MeSH
- kyseliny indoloctové chemie MeSH
- lidé MeSH
- oxadiazoly * chemická syntéza chemie farmakologie MeSH
- oxidační stres účinky léků MeSH
- thioketony * chemická syntéza chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- Publikační typ
- abstrakt z konference MeSH