Chem Biol Drug Des. 2009 Aug 19; Li F, Yin C, Chen J, Liu J, Xie X, Zhang AMono- and bis-indolomorphinans were synthesized through a multi-step synthetic approach from the alkaloid, thebaine, to further explore the C-ring SAR (structure-activity relationship) of morphinan scaffold. Both mono-indoles displayed good binding affinity and selectivity for the delta receptor, with compound 6b possessed the highest K(i) value of 1.45 nm at this receptor. Bisindolomorphinans 7a,b did not have appreciable affinity for both delta and kappa receptors, but moderate binding at the mu receptor was observed. Functional assays indicated that the newly synthesized mono-indole 6b was delta-agonist, opposite to the delta-antagonist profile of naltrindole. Bisindoles 7a,b were mu-agonists. This work further confirms that the phenol component in opioids is essential for higher binding to the opioid receptors. The different binding ability, receptor selectivity, and the functional activity profiles of naltrindole 2, monoindole 6b, and bisindole 7b clearly indicated that they interact with the opioid receptors in different modes.

J Pharm Biomed Anal. 2009 Jul 22; Sun N, Wen J, Lu G, Hong Z, Fan G, Wu Y, Sheng C, Zhang WIodiconazole is a very potent antifungal agent used to treat serious fungal infections. After transdermal administration, several factors affect the exposure of iodiconazole, resulting in large variability and demanding further elucidation of drug distribution. For determination of iodiconazole in dermal microdialysate, a new, efficient, reliable and robust ultra-fast liquid chromatography (UFLC, Shimadzu) assay using UV detection at 230nm has been developed and validated. Iodiconazole was separated on a Shimadzu Prominence UFLC C18 column (2.2mum, 50mmx2.0mm i.d.) using acetonitrile-0.025% triethylamine solution, adjusted to pH 3.6 with phosphoric acid (65:35, v/v), at a flow rate of 0.5ml/min. The retention time was 1.37min for iodiconazole and 1.78min for the internal standard, an isomeric compound of iodiconazole. Intra- and inter-day precision ranged from 5.3% to 7.8% and 3.7% to 8.4%, respectively. The UFLC method was used to measure iodiconazole concentrations in microdialysis samples obtained during the calibration of laboratory-made linear probes. The validation and sample analysis results show that the method is precise, accurate and well suited to support the dermal microdialysis experiments.

Life Sci. 2009 Aug 17; Wang SB, Yang XY, Tian S, Yang HG, Du GHAIMS: The present study was to evaluate the beneficial effect of salvianolic acid A (SAA) on the alterations in vascular reactivity of streptozotocin (STZ) diabetic rats. MAIN METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60mg/kg). Following 16weeks of SAA treatment (1mg/kg/day), thoracic aortic rings of rats were mounted in organ baths. Contractile responses to noradrenaline (NA) and KCl and relaxant responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed. KEY FINDINGS: Loss of weight, hyperglycemia, elevated content of malondialdehyde (MDA) and decline of total antioxidant capacity (TAC) were observed in diabetic rats. SAA could improve these metabolic and biochemical abnormalities. Compared to the control, the maximum contraction (E(max)) to NA, but not sensitivity (pD(2)), significantly elevated in diabetic aortas, which was prevented by SAA treatment. However, the response of rat aortas to KCl (E(max) and pD(2)) did not altered either in diabetic group or SAA treatment compared with that of normal control group. We also observed the significant decrease in relaxation to ACh rather than SNP in diabetic group compared with controls. And SAA treatment could revert the ACh response. Significance: It is concluded that oral administration of SAA can significantly improve glucose metabolism and inhibit oxidative injury as well as protect impaired vascular responsiveness in STZ-induced diabetic rats.