611-36-9Relevant articles and documents
HPLC-based bioactivity profiling of plant extracts: A kinetic assay for the identification of monoamine oxidase-A inhibitors using human recombinant monoamine oxidase-A
Dittmann, Kathrin,Riese, Ulrike,Hamburger, Matthias
, p. 2885 - 2891 (2004)
An assay for the HPLC-based search for monoamine oxidase-A (MAO-A) inhibitors in plant extracts was established. It combines human recombinant MAO-A, expressed as GST-fusion protein in yeast, with a kinetic measurement of the conversion of kynuramine to 4-hydroxyquinoline. Substrate selectivity and kinetic parameters of the GST-fusion protein were comparable to the wild-type enzyme. The applicability of the assay to HPLC-based activity profiling was tested with plant extracts spiked with small amounts of known MAO inhibitors.
In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks
Wagmann, Lea,Brandt, Simon D.,Kavanagh, Pierce V.,Maurer, Hans H.,Meyer, Markus R.
, p. 84 - 93 (2017)
Tryptamines have emerged as new psychoactive substances (NPS), which are distributed and consumed recreationally without preclinical studies or safety tests. Within the alpha-methylated tryptamines, some of the psychoactive effects of the prototypical alpha-methyltryptamine (AMT) have been described decades ago and a contributing factor of its acute toxicity appears to involve the inhibition of monoamine oxidase (MAO). However, detailed information about analogs is scarce. Therefore, thirteen AMT analogs were investigated for their potential to inhibit MAO. An in vitro assay analyzed using hydrophilic interaction liquid chromatography–high resolution-tandem mass spectrometry was developed and validated. The AMT analogs were incubated with recombinant human MAO-A or B and kynuramine, a non-selective MAO substrate to determine the IC50values. The known MAO-A inhibitors 5-(2-aminopropyl)indole (5-IT), harmine, harmaline, yohimbine, and the MAO-B inhibitor selegiline were tested for comparison. AMT and all analogs showed MAO-A inhibition properties with IC50values between 0.049 and 166?μM, whereas four analogs inhibited also MAO-B with IC50values between 82 and 376?μM. 7-Me-AMT provided the lowest IC50value against MAO-A comparable to harmine and harmaline and was identified as a competitive MAO-A inhibitor. Furthermore, AMT, 7-Me-AMT, and nine further analogs inhibited MAO activity in human hepatic S9 fraction used as model for the human liver which expresses both isoforms. The obtained results suggested that MAO inhibition induced by alpha-methylated tryptamines might be clinically relevant concerning possible serotonergic and adrenergic effects and interactions with drugs (of abuse) particularly acting as monoamine reuptake inhibitors. However, as in vitro assays have only limited conclusiveness, further studies are needed.
Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells
Mendes, Eduarda,Cadoni, Enrico,Carneiro, Filipa,Afonso, Marta B.,Brito, Hugo,Lavrado, Jo?o,dos Santos, Daniel J. V. A.,Vítor, Jorge B.,Neidle, Stephen,Rodrigues, Cecília M. P.,Paulo, Alexandra
, p. 1325 - 1328 (2019/06/21)
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline
UVA photoinduced yeast protein modifications by methylene blue and naproxen
Bracchitta, Giuseppina,Catalfo, Alfio,De Guidi, Guido
, p. 967 - 973 (2013/09/12)
UVA photosensitization by methylene blue (MB) or by naproxen (NAP) towards cell proteins in yeast Saccharomyces cerevisiae was investigated in order to compare this system with two simpler models, such as free Trp in solution and as a component of bovine and human serum albumin. The process was studied by monitoring protein tryptophan (Trp) residue integrity. The sensitized photodegradation of proteins resulted in different degrees of Trp damage with different Trp (photo)-products. Indeed, many of these Trp derivatives are diagnostic for the photosensitization mechanism and some of them were obtained from cells by UVA photosensitization for the first time in this work. The analysis of quantum yields of photoproduct distribution allowed us to weigh up the type I/II contribution on a UVA photosensitization mechanism. The UVA mediated generation of these Trp derivatives is consistent with the occurrence of singlet oxygen formation (almost dominant in MB), and photoionization (significant in NAP) within the protein matrix. The results obtained in the case of this more complex system (cell) are in agreement with the two simpler models recently studied in our lab. The quantum yields of Trp photoinduced degradation, as well as of its photoproducts formation, decrease with increasing the complexity of the investigated target. The Royal Society of Chemistry and Owner Societies 2013.
