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ACS Omega Nov 2023The reaction of either 2-aminophenol or 2-(-methylamino)phenol with 1,2-difluoro-4,5-dinitrobenzene and sodium carbonate in EtOH gives 2,3-dinitrophenoxazines. One nitro...
The reaction of either 2-aminophenol or 2-(-methylamino)phenol with 1,2-difluoro-4,5-dinitrobenzene and sodium carbonate in EtOH gives 2,3-dinitrophenoxazines. One nitro group, conjugated to the aryl ether, was displaced from 2,3-dinitro-10-methylphenoxazine with different nucleophiles: BuNH, KOEt, and KOH. The reaction of 2-aminothiophenol with 1,2-difluoro-4,5-dinitrobenzene under the same conditions gives 2,3-dinitrophenothiazine. This reacted with BuNH forming 2-butylamino-3-nitrophenothiazine. The dihedral angles of the different compounds are compared.
PubMed: 38027375
DOI: 10.1021/acsomega.3c06461 -
IUCrData Apr 2024The title compound, CHNS, crystallizes in space group 2/ with four mol-ecules in the asymmetric unit. The heterocyclic mol-ecule is quasi-planar with a dihedral angle...
The title compound, CHNS, crystallizes in space group 2/ with four mol-ecules in the asymmetric unit. The heterocyclic mol-ecule is quasi-planar with a dihedral angle between the phenyl rings on the periphery of the mol-ecule of 1.73 (19)°. Short H⋯S (2.92 Å) and C-H⋯π [2.836 (3) Å] contacts are observed in the crystal with shorted -π stacking distances of 3.438 (3) Å along the axis. Surprisingly, and unlike a closely related material, this mol-ecule readily forms large crystals by sublimation and by slow evaporation from di-chloro-methane. The maximum absorbance in the UV-Vis spectrum is at 533 nm. Emission was measured upon excitation at 533 nm with a fluorescence λ of 658 nm and cutoff of 900 nm.
PubMed: 38721004
DOI: 10.1107/S2414314624003572 -
RSC Advances Jul 2023Compounds PTZ-MBZ (methyl 3-(10-phenothiazin-10-yl)benzoate) and DMAC-MBZ (methyl 3-(9,9-dimethylacridin-10(9)-yl)benzoate) were conveniently synthesized, and they...
Compounds PTZ-MBZ (methyl 3-(10-phenothiazin-10-yl)benzoate) and DMAC-MBZ (methyl 3-(9,9-dimethylacridin-10(9)-yl)benzoate) were conveniently synthesized, and they exhibited TADF properties with lifetimes of 0.80 and 2.17 μs, respectively. The spatially separated highest occupied molecular orbital and lowest unoccupied molecular orbital resulted in a very small singlet-triplet energy gap of 0.0152 eV and 0.0640 eV, respectively. Thermally activated delayed fluorescence materials with short lifetime could be used as promising luminescent materials for organic light-emitting diodes.
PubMed: 37456544
DOI: 10.1039/d3ra03289b -
Science Advances Oct 2023Cancers in the central nervous system resist therapies effective in other cancers, possibly due to the unique biochemistry of the human brain microenvironment composed...
Cancers in the central nervous system resist therapies effective in other cancers, possibly due to the unique biochemistry of the human brain microenvironment composed of cerebrospinal fluid (CSF). However, the impact of CSF on cancer cells and therapeutic efficacy is unknown. Here, we examined the effect of human CSF on glioblastoma (GBM) tumors from 25 patients. We found that CSF induces tumor cell plasticity and resistance to standard GBM treatments (temozolomide and irradiation). We identified nuclear protein 1 (NUPR1), a transcription factor hampering ferroptosis, as a mediator of therapeutic resistance in CSF. NUPR1 inhibition with a repurposed antipsychotic, trifluoperazine, enhanced the killing of GBM cells resistant to chemoradiation in CSF. The same chemo-effective doses of trifluoperazine were safe for human neurons and astrocytes derived from pluripotent stem cells. These findings reveal that chemoradiation efficacy decreases in human CSF and suggest that combining trifluoperazine with standard care may improve the survival of patients with GBM.
Topics: Humans; Glioblastoma; Trifluoperazine; Brain Neoplasms; Temozolomide; Chemoradiotherapy; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37878712
DOI: 10.1126/sciadv.adf1332 -
Nature Communications Sep 2023Preventing tau aggregation is a potential therapeutic strategy in Alzheimer's disease and other tauopathies. Recently, liquid-liquid phase separation has been found to...
Preventing tau aggregation is a potential therapeutic strategy in Alzheimer's disease and other tauopathies. Recently, liquid-liquid phase separation has been found to facilitate the formation of pathogenic tau conformations and fibrillar aggregates, although many aspects of the conformational transitions of tau during the phase transition process remain unknown. Here, we demonstrate that the tau aggregation inhibitor methylene blue promotes tau liquid-liquid phase separation and accelerates the liquid-to-gel transition of tau droplets independent of the redox activity of methylene blue. We further show that methylene blue inhibits the conversion of tau droplets into fibrils and reduces the cytotoxicity of tau aggregates. Although gelation slows down the mobility of tau and tubulin, it does not impair microtubule assembly within tau droplets. These findings suggest that methylene blue inhibits tau amyloid fibrillization and accelerates tau droplet gelation via distinct mechanisms, thus providing insights into the activity of tau aggregation inhibitors in the context of phase transition.
Topics: Humans; Methylene Blue; Alzheimer Disease; Amyloidogenic Proteins; Cytoskeleton; Phase Transition
PubMed: 37673952
DOI: 10.1038/s41467-023-41241-6 -
Journal of Audiology & Otology Jan 2024There have been few investigations on the epidemiology, etiology, and medical management of acute unilateral vestibulopathy (AUV). Short-term pharmaceutical resolutions... (Review)
Review
There have been few investigations on the epidemiology, etiology, and medical management of acute unilateral vestibulopathy (AUV). Short-term pharmaceutical resolutions include vestibular symptomatic suppressants, anti-emetics, and some cause-based therapies. Anticholinergics, phenothiazines, antihistamines, antidopaminergics, benzodiazepines, and calcium channel antagonists are examples of vestibular suppressants. Some of these medications may show their effects through multiple mechanisms. In contrast, N-acetyl-L-leucine, Ginkgo biloba, and betahistine improve central vestibular compensation. Currently, AUV pathophysiology is poorly understood. Diverse hypotheses have previously been identified which have brought about some causal treatments presently used. According to some publications, acute administration of anti-inflammatory medications may have a deleterious impact on both post-lesional functional recovery and endogenous adaptive plasticity processes. Thus, some authors do not recommend the use of corticosteroids in AUV. Antivirals are even more contentious in the context of AUV treatment. Although vascular theories have been presented, no verified investigations employing anti-clotting or vasodilator medications have been conducted. There are no standardized treatment protocols for AUV to date, and the pharmacological treatment of AUV is still questionable. This review addresses the most current developments and controversies in AUV medical treatment.
PubMed: 37953517
DOI: 10.7874/jao.2023.00066