Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A2A.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC50 values of 2.30 and 2.45 µM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A , but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors.

A liquid chromatography-tandem mass spectrometry method for pharmacokinetics and tissue distribution of a camptothecin quaternary derivative in rats.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to identify and quantify the camptothecin quaternary derivative CPT8 for application in pharmacokinetics and tissue distribution studies. Rat plasma and tissue samples were extracted with methanol by using camptothecin as the internal standard (IS). Chromatographic separation of CPT8 and the IS was achieved using a Hypersil GOLD C18 column, with a flow rate of 1.0 mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in the positive ion mode and by applying multiple reaction monitoring. The MS/MS ion transitions were monitored at m/z 484.3-361.2 for CPT8 and m/z 349.0-305.2 for the IS (CPT). A calibration curve was constructed using CPT8 concentrations ranging from 2.5 ng/mL to 2500 ng/mL (r>0.993). The efficiency of CPT8 extraction from plasma and tissue samples ranged from 91.23% to 105.4%. Intra- and inter-day precision (relative standard deviation) values were 0.21% and 7.25%, respectively. No matrix effects were observed. The freeze-thaw stability, post-extraction stability, and stability following short- and long-term storage at low temperatures ranged from 84.12% to 108.2%. The preclinical data obtained using this method is expected to facilitate future clinical investigations of CPT8.

[Distribution and accumulation of vindoline, catharanthine and vinblastine in Catharanthus roseus cultivated in China].

OBJECTIVE: The content of vindoline, catharanthine and vinblastine in the root, stem, leaf, flower and fruit of Catharanthus roseus at various developmental stages were determined, and the biomass allocation was also determined to find the best harvest time. METHOD: The content of vindoline, catharanthine and vinblastine in the root, stem, leaf, flower and fruit of C. roseus were determined by HPLC. RESULT: The content of these alkaloids were influenced by season and it varied in the different tissues of the plant. The content of vindoline and catharanthine in the leaves were the highest, and there was no vindoline detected in the root, but the content of vinblastine in the flower was the highest; the content of vindoline and catharanthine reached the maximum between the August and September, and the content of vinblastine reached the highest after the September. The biomass was the highest in the initial stage of September. CONCLUSION: The best harvest time was in the initial stage of September.