63273-48-3Relevant articles and documents
Photoactivated thiazole-based DNA-cleaving agents: Dramatic change of recognition sequence: Depending on the number of thiazole units
Ninomiya,Satoh,Sugiyama,Shinomiya,Kuroda
, p. 1825 - 1826 (1996)
By increasing the number of thiazole units in the photoactive DNA cleaving compounds, 4-(3-dimethylsulfoniopropyl- aminocarbonyl)-2-[2-(4-nitrobenzoylamino)ethyl]oligo-thiazole, from one or two to three, the specificity of their DNA cleavage was dramatically altered from 5'-AAATN-3' (N ≠ G) to 5'-GG-3'.
Phenothiazine-Tacrine Heterodimers: Pursuing Multitarget Directed Approach in Alzheimer's Disease
Gorecki, Lukas,Uliassi, Elisa,Bartolini, Manuela,Janockova, Jana,Hrabinova, Martina,Hepnarova, Vendula,Prchal, Lukas,Muckova, Lubica,Pejchal, Jaroslav,Karasova, Jana Z.,Mezeiova, Eva,Benkova, Marketa,Kobrlova, Tereza,Soukup, Ondrej,Petralla, Sabrina,Monti, Barbara,Korabecny, Jan,Bolognesi, Maria Laura
, p. 1698 - 1715 (2021/05/10)
Since 2002, no clinical candidate against Alzheimer's disease has reached the market; hence, an effective therapy is urgently needed. We followed the so-called "multitarget directed ligand"approach and designed 36 novel tacrine-phenothiazine heterodimers which were in vitro evaluated for their anticholinesterase properties. The assessment of the structure-activity relationships of such derivatives highlighted compound 1dC as a potent and selective acetylcholinesterase inhibitor with IC50 = 8 nM and 1aA as a potent butyrylcholinesterase inhibitor with IC50 = 15 nM. Selected hybrids, namely, 1aC, 1bC, 1cC, 1dC, and 2dC, showed a significant inhibitory activity toward τ(306-336) peptide aggregation with percent inhibition ranging from 50.5 to 62.1%. Likewise, 1dC and 2dC exerted a remarkable ability to inhibit self-induced Aβ1-42 aggregation. Notwithstanding, in vitro studies displayed cytotoxicity toward HepG2 cells and cerebellar granule neurons; no pathophysiological abnormality was observed when 1dC was administered to mice at 14 mg/kg (i.p.). 1dC was also able to permeate to the CNS as shown by in vitro and in vivo models. The maximum brain concentration was close to the IC50 value for acetylcholinesterase inhibition with a relatively slow elimination half-time. 1dC showed an acceptable safety and good pharmacokinetic properties and a multifunctional biological profile.
Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols
Zhang, Wen,Carpenter, Keith L.,Lin, Song
supporting information, p. 409 - 417 (2019/11/25)
Riboflavin-derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin-catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O2 and an oxidant and generating H2O2 as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen-atom abstraction.
