ABSTRACT
A new series of aromatic ester and carbamate derivatives of 2-(1H-imidazol-1-yl)-1-phenylethanol were synthesized and evaluated for their antifungal activity towards Candida albicans and non-albicans Candida species strains. The aromatic biphenyl ester derivatives 6a-c were more active than the reference compound fluconazole. 6c possesses a MIC mean values of 1.7 ± 1.4 µg mL(-1)vs C. albicans and 1.9 ± 2.0 µg mL(-1)vs non-albicans Candida species strains. The racemic mixtures of 6a, b were purified to afford the pure enantiomers. The (-) isomers were up to 500 times more active than (+) isomers. (-)-6a and (-)-6b were thirty and ninety times more active than fluconazole towards C. krusei strain respectively. The racemates of 6a-c showed low cytotoxicity against human monocytic cell line (U937) with 6a demonstrating a CC(50) greater than 128 µg mL(-1).
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Candida/drug effects , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/pharmacology , Antifungal Agents/chemical synthesis , Candida albicans/drug effects , Candidiasis/drug therapy , Cell Line , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , Imidazoles/pharmacology , Microbial Sensitivity Tests , Phenylethyl Alcohol/chemical synthesisABSTRACT
The best of both: SIRT1/2 inhibitors were developed by combining chemical features of selisistat (SIRT1-selective inhibitor; blue) and carprofen (anti-inflammatory drug; red). The most potent compound (shown) increased acetyl-p53 and acetyl-α-tubulin levels, and induced slight apoptosis at 50â µM in U937 cells, differently from selisistat and carprofen.
Subject(s)
Carbazoles/chemistry , Carbazoles/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacology , Neoplasms/enzymology , Sirtuin 1/antagonists & inhibitors , Sirtuin 2/antagonists & inhibitors , Acetylation/drug effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Humans , Neoplasms/drug therapy , Sirtuin 1/metabolism , Sirtuin 2/metabolism , Tubulin/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
The favoured protonation sites leading to isomeric toluenium ions have been assayed, envisaging the mildest possible route for proton transfer to naked toluene.
Subject(s)
Protons , Toluene/chemistry , Deuterium/chemistry , Gases/chemistry , Hydrogen/chemistry , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Spectroscopy/standards , Models, Chemical , Reference Standards , Water/chemistryABSTRACT
The electroencephalographic (EEG) effects of two choline pivaloyl esters, [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium iodide (1) and [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (2), were evaluated in scopolamine-treated or nucleus basalis magnocellularis (NBM) lesioned rats. In scopolamine-treated animals, Compounds 1 and 2 prevented or reduced EEG effects, such as increased amplitude of total spectra and high-voltage spindle (HVS) activity as well. Furthermore, choline esters showed a noticeable effectiveness in reversing the EEG changes produced in rats by AMPA-induced lesion of NBM. Indeed, Compounds 1 and 2 were able to induce EEG desynchronisation, a significant decrease in the total EEG power (0.25-16 Hz) and in the lower frequency delta and theta bands (0.25-3 and 3-6 Hz, respectively). The EEG effects produced by Compounds 1 and 2 were well comparable with that evoked by Tacrine, used as a reference compound. The results of the present work allow us to put forward the hypothesis that the EEG effects observed are most likely mediated through the stimulation of the cholinergic neurotransmission ensuing from enhanced cerebral levels of acetylcholine (ACh) consequent upon acetylcholinesterase (AChE) inhibition by choline pivaloyl esters.
