Ethyl 4-(4-bromo­phen­yl)-6-r-phenyl-2-oxocyclo­hex-3-ene-1-t-carboxyl­ate

In the title compound, C21H19BrO3, the cyclo­hexene ring adopts an envelope conformation, with all substituents equatorial. The plane through its five coplanar atoms makes dihedral angles of 28.88 (10) and 71.94 (10)° with the bromo­benzene and phenyl rings, respectively. The dihedral angle between the latter two rings is 51.49 (15)°. Inter­molecular C—H⋯O hydrogen bonds are found in the crystal structure; a C—H⋯π inter­action is also present

Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation

Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a new series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil–hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD

Conformation of Alkali Metal Ion−Benzo-12-Crown‑4 Complexes Investigated by UV Photodissociation and UV−UV Hole-Burning Spectroscopy

We measure UV photodissociation (UVPD) spectra of benzo-12-crown-4 (B12C4) complexes with alkali metal ions, M+·B12C4 (M = Li, Na, K, Rb, and Cs), in the 36300−37600 cm−1 region. Thanks to the cooling of ions to ∼10 K, all the M+·B12C4 complexes show sharp vibronic bands in this region. For UV−UV hole-burning (HB) spectroscopy, we first check if our experimental system works well by observing UV−UV HB spectra of the K+ complex with benzo-18-crown-6 (B18C6), K+·B18C6. In the UV−UV HB spectra of the K+·B18C6 complex, gain signals are also observed; these are due to vibrationally hot K+·B18C6 complex produced by the UV excitation of cold K+·B18C6 complex. Then we apply UV−UV HB spectroscopy to the M+·B12C4 complexes, and only one conformer is found for each complex except for the Li+ complex, which has two conformers. The vibronic structure around the origin band of the UVPD spectra is quite similar for all the complexes, indicating close resemblance of the complex structure. The most stable structures calculated for the M+·B12C4 (M = Li, Na, K, Rb, and Cs) complexes also have a similar conformation among them, which coincides with the UVPD results. In these conformers the metal ions are too big to be included in the B12C4 cavity, even for the Li+ ion. In solution, it was reported that 12-crown-4 (12C4) shows the preference of Na+ ion among alkali metal ions. From the similarity of the structure for the M+·B12C4 complexes, it is suggested that the solvation of free metal ions, not of the M+·12C4 complexes, may lead to the selectivity of Na+ ion for 12C4 in solution.This work was partly supported by JSPS KAKENHI Grant Number 16H04098

Treatment of Gaucher disease with an enzyme inhibitor

The hypothesis is offered predicting that Caucher patients could be treated with a drug that slows the synthesis of glucosylceramide, the lipid that accumulates in this disorder. The present therapeutic approach involves augmenting the defective enzyme, glucosylceramide β-glucosidase, with exogenous β-glucosidase isolated from human tissue. This spectacularly expensive mode of treatment should be replaceable with a suitable enzyme inhibitor that simply slows formation of the lipid and matches the rate of synthesis with the rate of the defective, slowly working β-glucosidase. Several drugs that possess this ability are available, the best known of which is 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's substrate and product. PDMP has been found to be effective in mice, rats, fish, and a wide variety of cultured cells. Its use, at suitable dosages, seems to be harmless, although long-term tests have not been made. The lack of suitable animal models of Gaucher disease has made it difficult to test the hypothesis adequately, but PDMP does rapidly lower the levels of glucosylceramide in normal animal tissues and the animals evidently do well with the lowered levels of glucosylceramide and its more complex glycolipid metabolites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45689/1/10719_2004_Article_BF00731489.pd

Tetrathiotetracene thin film morphology and electrical properties

The electrical properties of organic thin films are determined by their chemical constituents and the morphology of the films deposited. In this paper the morphology of vacuum sublimed (7∙10-6 mbar) tetrathiotetracene (TTT) thin films is shown to be strongly affected by the thermal deposition temperature (222-350 K) and rate of deposition. Mostly needle-like morphologies are identified by scanning electron microscopy. Optimal TTT purity (a pre-requisite for device preparation via subsequent oxidation) is evidenced by their initially low electrical conductivity. Altering the TTT morphology, by variation of the evaporation parameters, strongly affects this base electrical conductivity. Four probe conductivity measurements and charge extraction by linear increasing voltage methods are used to characterize film electrical properties. In-plane conductivity of up to 7.03∙10-5 S/cm is achieved for pure TTT thin films. Subsequent aerial oxidation resulted in a 3.4-fold increase in electrical conductivity

Porto-systemic shunt using adrenal vein as a conduit; an alternative procedure for spleno – renal shunt

PubMed ID: 17555599Background. Currently, portal hypertension is still big problem for the patients with serious liver diseases. Variceal bleeding is one of the most important complications of portal hypertension. In case of failure of endoscopic and combined medical treatments, surgical decompressive shunts are required. We emphasized an alternative splenorenal shunt procedure using adrenal vein as a conduit. Case presentation. A 26-year-old male suffered from recurrent variceal bleeding was considered for surgical therapy. Although we planned to perform a distal splenorenal shunt procedure, it was observed to be difficult. Therefore left adrenal vein was used as a conduit between left renal vein and splenic vein after splenic artery was ligated. He did well and was discharged from the hospital on the postoperative day 6. In the follow up period for nine months, endoscopic and ultrasonographic examinations were normal. Conclusion. We concluded that, in case of failure to perform distal splenorenal shunt due to technical problems, alternative porto-systemic shunt procedure using the adrenal vein as a vascular conduit can be safely employed. © 2007 Aydin et al; licensee BioMed Central Ltd

Effects of the glucolipid synthase inhibitor, P4, on functional and phenotypic parameters of murine myeloma cells

This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 μM P4 (the IC50 concentration). Both cytostatic and cytotoxic inhibition was observed with tumour cell metabolic activity and clonogenic potential reduced to 42% and 14% of controls, respectively, and viability reduced to 52%. A dose-dependent increase in cells undergoing apoptosis (from 7% to 26%) was also found. P4 induced a decrease in the number of cells expressing H-2 Class I and CD44, and a large increase in cells expressing H-2 Class II and the IgG2b paraprotein. It did not affect surface expression of CD45 or CD54 (ICAM-1). Based on these alterations in tumour cell growth, adhesion molecule expression and potential immunogenicity, it is anticipated that P4 will provide a novel therapeutic approach for the treatment of multiple myeloma. In addition, given that essentially all tumours rely heavily on overexpressed or abnormal glucosphingolipids for growth, development and metastasis, glucolipid synthase inhibitors may prove to be universally effective anti-cancer agents. © 1999 Cancer Research Campaig