Flavin Mononucleotide-Mediated Formation of Highly Electrically Conductive Hierarchical Monoclinic Multiwalled Carbon Nanotube-Polyamide 6 Nanocomposites.

Although the multiwalled carbon nanotube (MWNT) is a promising material for use in the production of high electrical conductivity (σ) polymer nanocomposites, its tendency to aggregate and distribute randomly in a polymer matrix is a problematic issue. In the current study, we developed a highly conductive and monoclinically aligned MWNT-polyamide 6 (PA) nanocomposite containing interfacing flavin moieties. In this system, the flavin mononucleotide (FMN) initially serves as a noncovalent aqueous surfactant for individualizing MWNTs in the form of FMN-wrapped MWNTs (FMN-MWNT), and then partially decomposed FMN (dFMN) induces crystallization of the PA on the MWNTs. The results of experiments performed using material subjected to partial dissolution of PA matrix show that the nanocomposite PA-dFMN-MWNT, formed by melt extrusion of PA and dFMN-MWNT, contains a three-dimensional monoclinic MWNT network embedded in an equally monoclinic PA matrix. An increase in monoclinic network promoted by an increase in the content of MWNT increases σ of the nanocomposite up to 100 S/m, the highest value reported for a polymer-MWNT nanocomposite. X-ray diffraction along with transmission electron microscopy reveal that the presence of dFMN induces the formation of monoclinic PA on dFMN-MWNT. The high σ of the PA-dFMN-MWNT nanocomposite is also a consequence of a minimization of defect formation of MWNT by noncovalent functionalization. Hierarchical structural ordering, yet individualization of MWNTs, provides a viable strategy to improve the physical property of nanocomposites.

Indole-Substituted Benzothiazoles and Benzoxazoles as Selective and Reversible MAO-B Inhibitors for Treatment of Parkinson's Disease.

To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 28 nM with no apparent effect on MAO-A activity at 10 µM. Based on the reversibility assay, compound 5b turned out to be fully reversible with over 95% of recovery of enzyme activity after washout of the compound. Compound 5b showed a reasonable stability in human liver microsomes and did not affect the activities of CYP isozymes, suggesting an absence of high-risk drug-drug interaction. In an in vivo MPTP-induced animal model of Parkinson's disease, oral administration of compound 5b showed neuroprotection of nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevention of MPTP-induced parkinsonism as revealed by motor behavioral assay of vertical grid test. In summary, the novel, reversible, and selective MAO-B inhibitor compound 5b was synthesized and characterized. We propose compound 5b as an effective therapeutic compound for relieving parkinsonism.