Influence of extract ofEleutherococcus and eleutherosides A,B, C,D + E on release and metabolism of arachidonic acid

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 22, No. 7, pp. 776–779, July, 1988.     

Synthesis and characterization of functional elastomeric poly(ester amide) co-polymers

A new family of random co-poly(ester amides)s (co-PEAs) having reactive pendant functional carboxylic acid groups were synthesized by co-polycondensation of di-p-toluenesulfonic acid salts of bis-(L-alpha-amino acid (L-leucine and/or L-phenylalanine)) alpha,omega-alkylene diesters with active diesters of dicarboxylic acids using di-p-toluenesulfonic acid salt of L-lysine benzyl ester as a co-monomer. The lateral benzyl ester groups in the L-lysine segment of co-PEAs were subsequently transformed into free COOH groups by catalytic hydrogenolysis using Pd black as a catalyst. The co-PEA-based polyacids obtained, as well as the original co-PEA having lateral benzyl ester groups were characterized by standard methods. In vitro biodegradation studies in the presence of hydrolases like alpha-chymotrypsin and lipase showed significant enzymatic-catalyzed biodegradation of these co-PEAs. These co-PEA-based polyacids were used for covalent attachment of iminoxyl radicals (4-amino-TEMPO) and in vitro biodegradation of 4-aminoTEMPO attached polymer was studied along with releasing kinetic of iminoxyl radical.     

A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells

Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types.     

Synthesis and antioxidant activity of 1-(4-fluorophenyl)-1-alkyl-2-phenyl-3-morpholinopropan-1-ol hydrochlorides

Reactions of 4-fluorophenyl-β-morpholinopropiophenones with various Grignard reagents in anhydrous ether produced new tertiary aminoalcohols, 1-(4-fluorophenyl)-1-alkyl-2-phenyl-3-morpholinopropan-1-ols, that can be regarded as trihexyphenidyl (cyclodol) analogs. The antioxidant properties of the synthesized compounds were studied using a photochemiluminescence analytical method. It is established that the synthesized compounds exhibit antioxidant activity, the intensity of which depends on the length of the alkyl chain in the para-position of the benzene ring.