1210-56-6Relevant articles and documents
6-Hydroxy- and 6-methoxy-β-carbolines as acetyl- and butyrylcholinesterase inhibitors
Schott, Yvonne,Decker, Michael,Rommelspacher, Hans,Lehmann, Jochen
, p. 5840 - 5843 (2006)
In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on β-carbolines (BCs). 6-Oxygenated β-carboline and β-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine.
Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease
Feng, Feng,Jiang, Pan,Li, Qi,Liao, Qinghong,Liu, Wenyuan,Qu, Wei,Sun, Haopeng,Yan, Yuhui,Zhao, Yifan
, (2020/04/22)
Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity. Herein, a series of carboline-cinnamic acid hybrids was designed and synthesized to obtain new multifunctional molecules with low toxicity and good physicochemical properties. In particular, e3 and e12 exhibited significant inhibition of Aβ aggregation (inhibitory rate at 25 μM: 65% and 72% respectively), moderate BuChE inhibition, excellent neuroprotective effects and low neurotoxicity. Furthermore, in the AD mice model, e3 and e12 could restore learning and memory function to a comparable level to that of the control and did not exhibit any acute toxicity in vivo at a relatively high dose of 600 mg/kg. Thus, these new compounds can be further studied as multifunctional molecules for AD.
Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors
Cuny, Gregory D.,Ulyanova, Natalia P.,Patnaik, Debasis,Liu, Ji-Feng,Lin, Xiangjie,Auerbach, Ken,Ray, Soumya S.,Xian, Jun,Glicksman, Marcie A.,Stein, Ross L.,Higgins, Jonathan M.G.
scheme or table, p. 2015 - 2019 (2012/04/05)
Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure-activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented.
Isoharmine revisited: Thermal rearrangement of a 3-cyanomethyl-2- vinylindole
Sapi, Janos,Patigny, Dominique,Laronze, Jean-Yves
, p. 361 - 364 (2007/10/03)
Thermolysis of 2-vinylindole derivative (1) led to indolylacrylonitrile (6) instead of β-carboline alkaloid isoharmine (4). Latter was prepared by following the conventional method and was fully characterized.
Electron Impact and Chemical Ionization Fragmentation of 5-Methoxytryptamine and Some 6-Methoxy-β-carbolines
Gynther, Jukka,Peura, Pekka,Salmi, Seija
, p. 849 - 860 (2007/10/02)
Electron impact (EI) and chemical ionization (CI) mass spectra of 5-methoxytryptamine (5-MT) and seven 6-methoxy-β-carbolines have been recorded and interpreted.Proposed fragmentation pathways are depicted on the basis of spectra of deuterium labelled analogs of 5-MT, 6-methoxy-1,2,3,4-tetrahydro-β-carboline (6-MeO-THBC) and 6-Methoxy-1-methyl-1,2,3,4-tetrahydro-β-carboline (6-MeO-1-Me-THBC).In the EI mass spectrum of 5-MT, the base peak m/z 160 is formed by the expulsion of CH4N.The positive ion so formed is suggested to have a quinolinium structure.In chemical ionization with CH4 as the reaction gas, the most abundant ion is produced by cleavage of NH3.The ion m/z 173 yields the base peak in the EI mass spectrum of 6-MeO-THBC.This ion is formed by a retro Diels-Alder reaction, an important fragmentation pathway of 6-MeO-1-Me-THBC, too. 6-MeO-harmalan easily loses one hydrogen atom in EI fragmentation followed by methyl loss from the methoxy group, this latter process yielding the base peak, m/z 197 in the EI mass spectrum of 6-MeO-harman.M+1 is the base peak in the CI mass spectra of all 6-MeO-β-carbolines.
