In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox™ assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 μM and a CC50 against MRC-5 of 67.4 μM.

• Klíčová slova
• 4-Hydroxyquinolin-2(1H)-ones, Antibiotic, Cytotoxicity, Genotoxicity, Mycobacterium tuberculosis, Tuberculosis,
• MeSH
• antituberkulotika chemická syntéza   chemie   farmakologie   MeSH
• chinolony chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• Mycobacterium bovis účinky léků   růst a vývoj   MeSH
• Mycobacterium tuberculosis účinky léků   růst a vývoj   MeSH
• racionální návrh léčiv * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-hydroxyquinolin-2(1H)-one MeSH Prohlížeč
• antituberkulotika MeSH
• chinolony MeSH

It has been suggested that weak 50/60 Hz [extremely low frequency (ELF)] magnetic fields (MF) could affect circadian biorhythms by disrupting the clock function of cryptochromes (the "cryptochrome hypothesis," currently under study). That hypothesis is based on the premise that weak (Earth strength) static magnetic fields affect the redox balance of cryptochromes, thus possibly their signaling state as well. An appropriate method for testing this postulate could be real time or short-term study of the circadian clock function of retinal cryptochromes under exposure to the static field intensities that elicit the largest redox changes (maximal "low field" and "high field" effects, respectively) compared to zero field. Positive results might encourage further study of the cryptochrome hypothesis itself. However, they would indicate the need for performing a similar study, this time comparing the effects of only slight intensity changes (low field range) in order to explore the possible role of the proximity of metal structures and furniture as a confounder under the cryptochrome hypothesis.

• MeSH
• cirkadiánní hodiny fyziologie   MeSH
• kryptochromy fyziologie   MeSH
• magnetické pole * MeSH
• retina fyziologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kryptochromy MeSH

Plant-derived smoke and certain smoke compounds improve seed germination and enhance seedling growth of many species. Thus, smoke-infused water and the active smoke-derived compounds have the potential to be used in different agricultural and horticultural applications. However, despite these interesting and potentially practical properties, it should also be ascertained whether such compounds may pose a health risk, particularly if they are to be used in the production of food or fodder crops. Amongst some of the aspects that would be important to understand are any possible genotoxic properties that the compounds may possess due to potential carry-over effects. Here, we report on a genotoxicity study of 3,4,5-trimethylfuran-2(5H)-one, a compound from plant-derived smoke previously shown to have germination inhibitory activity. Using two in vitro tests, namely the bacterial VITOTOX® test (with/without S9 metabolic activation) and the cytome assay on human C3A cells, no genotoxicity or toxicity was found. Furthermore, these results support a previous study where a related smoke-derived compound with germination promoting properties was investigated.

• Klíčová slova
• Butenolide, Cytome, VITOTOX,
• MeSH
• 4-nitrochinolin-1-oxid toxicita   MeSH
• benzopyreny toxicita   MeSH
• chinolony toxicita   MeSH
• furany farmakologie   MeSH
• hepatocyty cytologie   účinky léků   metabolismus   MeSH
• klíčení účinky léků   MeSH
• lidé MeSH
• luciferasy genetika   metabolismus   MeSH
• mutageny farmakologie   MeSH
• nádorové buněčné linie MeSH
• reportérové geny MeSH
• rostliny účinky léků   MeSH
• Salmonella typhimurium účinky léků   genetika   růst a vývoj   MeSH
• semena rostlinná účinky léků   růst a vývoj   MeSH
• SOS odpověď (genetika) účinky léků   MeSH
• testy genotoxicity MeSH
• transkripční faktory genetika   metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3,4,5-trimethylfuran-2(5H)-one MeSH Prohlížeč
• 4-nitrochinolin-1-oxid MeSH
• 4-nitroquinolone-1-oxide MeSH Prohlížeč
• benzopyreny MeSH
• chinolony MeSH
• furany MeSH
• luciferasy MeSH
• mutageny MeSH
• transkripční faktory MeSH