Conformationally restricted tricyclic analogues of lipophilic pyrido[2,3‐d]pyrimidine antifolates

The effect of conformational restriction of the C9‐N10 bridge on inhibitory potency and selectivity of trimetrexate against dihydrofolate reductase, was studied. Specifically three nonclassical tricyclic 1,3‐diamino‐8‐(3′,4′,5′‐trimethoxybenzyl)‐7,9‐dihydro‐pyrrolo[3,4‐c]pyrido[2,3‐d]pyrimidin‐6(5H,8H)‐one ( 4 ), 1,3‐diamino‐8‐(3′,4′,5′‐trimethoxybenzyl)‐9‐hydro‐pyrrolo[3,4‐c]pyrido[2,3‐d]pyrimidin‐6‐(8H)‐one ( 5 ) and 1,3‐diamino‐(8H)‐(3′,4′,5′‐trimethoxybenzyl)‐7,9‐dihydro‐pyrrolo[3,4‐c]pyrido[2,3‐d]pyrimidine ( 7 ) antifolates were synthesized. The tricyclic analogues 4 and 5 were obtained via the regiospecific cyclo‐condensation of the β‐keto ester 17 with 2,4,6‐triaminopyrimidine. The analogue 7 was obtained via reduction of the lactam 4 with borane in tetrahydrofuran. Compounds 4, 5 and 7 were evaluated as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii and rat liver. All three compounds were more selective than trimetrexate against Pneumocystis carinii dihydrofolate reductase and significantly more selective than trimetrexate against Toxoplasma gondii dihydrofolate reductase compared with rat liver dihydrofolate reductase.     

Determination of carboplatin in canine plasma by high‐performance liquid chromatography

Carboplatin is an antineoplastic drug administered to treat different tumoral conditions in canine oncology. The objective of this study was to validate a high‐performance chromatographic (HPLC) method which could be applied in canine pharmacokinetic studies. Following ultrafiltration using a Centrifree device, standards, quality controls and plasma samples were separated by isocratic reversed‐phase HPLC on an Inertsil ODS‐2 (250 × 4.6 mm i.d.) analytical column and quantified using UV detection at 220 nm. The mobile phase was potassium phosphate (pH 4.5), with a flow‐rate of 1.0 mL/min. The procedure produced a linear curve (r² > 0.999) over the concentration range 1–200 μg/mL. The lower limit of quantification was 1 μg/mL. The intra‐assay and inter‐assay precision was ～90%. The overall recovery was ～90%. The method was illustrated with a preliminary pharmacokinetic analysis on nine dogs treated with carboplatin at our hospital. Carboplatin disposition followed a monocompartmental structure in dogs and was characterized by a short half‐life (50 min). Copyright © 2009 John Wiley & Sons, Ltd.     

Europium(III) DOTA-tetraamide complexes as redox-active MRI sensors

PARACEST redox sensors containing the NAD(+)/NADH mimic N-methylquinolinium moiety as a redox-active functional group have been designed and synthesized. The Eu(3+) complex with two quinolinium moieties was nearly completely CEST-silent in the oxidized form but was "turned on" upon reduction with β-NADH. The CEST effect of the Eu(3+) complex containing only one quinolinium group was much less redox-responsive but showed an unexpected sensitivity to pH in the physiologically relevant pH range.     

Determination of propofol using high performance liquid chromatography in whole blood with fluorescence detection

High-performance liquid chromatography method for the determination of propofol has been developed and validated. Following a liquid extraction using ethyl acetate and hexane, samples were separated by reverse-phase high-performance liquid chromatography on an XBridge C(18) column and quantified using fluorescence detection at an excitation of 276 nm and an emission of 310 nm. The mobile phase was a mixture of water (pH 4.0) and acetonitrile, with a flow rate of 1.5 mL/min. The standard curve ranged from 5-2000 ng/mL. Intra- and inter-assay variability for propofol was less than 10%, and the average recovery was greater than 95%. This assay is suitable for use in pharmacokinetic studies.     

Asymmetric synthesis of sulfinamides using (-)-quinine as chiral auxiliary

A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.     

A method for the synthesis of 2-aminobenzoxazoles

A synthesis of 2-aminobenzoxazoles from the parent C–H compound is described. The procedure involves deprotonation at the 2-position of the benzoxazole and quenching the intermediate organolithium species with a halogen electrophile. The 2-halobenzoxazole is then treated in the same pot with an amine nucleophile to afford the desired product. The substrate scope and selectivity of the reaction are presented. The method is operationally simple and provides access to a variety of amine products bearing additional nucleophilic heteroatoms.     

Synthesis and characterization of colloidal fluorescent silver nanoclusters

Ultrasmall water-soluble silver nanoclusters are synthesized, and their properties are investigated. The silver nanoclusters have high colloidal stability and show fluorescence in the red. This demonstrates that like gold nanoclusters also silver nanoclusters can be fluorescent.     

Quality assessment of a formulated Chinese herbal decoction, Kaixinsan, by using rapid resolution liquid chromatography coupled with mass spectrometry: A chemical evaluation of different historical formulae

Kaixinsan is an ancient Chinese herbal decoction mainly prescribed for patients suffering from mental depression. This decoction was created by Sun Si-miao of Tang Dynasty (A.D. 600) in ancient China, and was composed of four herbs: Radix and Rhizome Ginseng, Radix Polygalae, Rhizoma Acori Tatarinowii and Poria. Historically, this decoction has three different formulations, each recorded at a different point in time. In this study, the chemical compositions of all three Kaixinsan formulae were analyzed. By using rapid resolution LC coupled with a diode-array detector and an ESI triple quadrupole tandem MS (QQQ-MS/MS), the Radix and Rhizome Ginseng-derived ginsenosides including Rb(1), Rd, Re, Rg(1), the Radix Polygalae-derived 3,6'-disinapoyl sucrose, the Rhizoma Acori Tatarinowii-derived α- and β-asarone and the Poria-derived pachymic acid were compared among the three different formulations. The results showed variations in the solubility of different chemicals between one formula and the others. This systematic method developed could be used for the quality assessment of this herbal decoction.