noscapine and hydrastine

Energy-dependent collision-induced dissociation (CID) of the dimers [2 M + Cat](+) of the noscapine and hydrastine stereoisomers was studied where Cat stands for Li(+), Na(+), K(+) and Cs(+) ions. These dimers were generated 'in situ' from the electrosprayed solution. The survival yield (SY) method was used for distinguishing the noscapine and hydrastine dimers. Significant differences were found between the characteristic collision energies (CE50, i.e. the collision energy necessary to obtain 50% fragmentation) of the homo- (R,R; S,S) and heterochiral (R,S; S,R) stereoisomers. To distinguish the enantiomer pairs L-, D-tyrosine ([M + Tyr + Cat](+)) and L-, D-lysine ([M + Lys + Cat](+)) were used as chiral selectors. Furthermore, these heterodimers [M + amino acid + Cat](+) were also applied to determine the stereoisomeric composition. It was found that the characteristic collision energy (CE50) of the noscapine and hydrastine homodimers ([2 M + Cat](+)) was inversely proportional to the ionic radius of the cations. Furthermore, the structures of the dimers [2 M + Cat](+) were studied by high level quantum chemical calculations.

Topics: Benzylisoquinolines; Cations; Dimerization; Lithium; Lysine; Models, Chemical; Noscapine; Quantum Theory; Sodium; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; Tandem Mass Spectrometry; Tyrosine

Functional versatility and elevated expression in cancers have promoted p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug targets. In this study, a series of novel 1-phenanthryl-tetrahydroisoquinoline analogues have been designed and synthesized as a novel class of small-molecule PAK4 inhibitors to fit into the cavity of PAK4. All of the target compounds were evaluated for their in vitro PAK4 inhibitory activities and antiproliferative activities. Lead optimization identified all the derivatives with more potency than the lead compound, especially compound 21a. Moreover, compound 21a significantly induced the cell cycle in the G1/S phase, and inhibited migration and invasion of MCF-7 cells via the regulation of the PAK4-LIMK1-cofilin signaling pathway. A molecular modeling study showed possible novel binding modes between 21a and PAK4 and provided a structural basis for further structure-guided design of PAK4 inhibitors.

Topics: Apoptosis; Benzylisoquinolines; Breast Neoplasms; Cell Cycle; Cell Movement; Cell Proliferation; Drug Design; Female; Humans; Indicators and Reagents; Lentivirus; MCF-7 Cells; Models, Molecular; Neoplasm Invasiveness; Noscapine; p21-Activated Kinases; Phenanthrenes; Protein Kinase Inhibitors; Tetrahydroisoquinolines

Topics: Benzylisoquinolines; Berberine Alkaloids; Chemistry, Pharmaceutical; Noscapine; Quinolines; Research

Topics: Alkaloids; Benzylisoquinolines; Berberine Alkaloids; Chemistry, Pharmaceutical; Noscapine; Quinolines; Research

Topics: Benzylisoquinolines; Biological Products; Dehydration; Edetic Acid; Hydrastis; Mercury; Noscapine; Quinolines

Topics: Alkaloids; Benzylisoquinolines; Hydro-Lyases; Noscapine; Polarography; Tetrahydroisoquinolines

Topics: Alkaloids; Benzylisoquinolines; Noscapine; Polarography