1. Novel skin permeation enhancers based on amino acid ester ionic liquid: Design and permeation mechanism
Luyao Zheng, Zhiyuan Zhao, Ye Yang, Yaming Li, Chengxiao Wang Int J Pharm. 2020 Feb 25;576:119031. doi: 10.1016/j.ijpharm.2020.119031. Epub 2020 Jan 15.
This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility. In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs).
2. Metal-free and regiospecific synthesis of 3-arylindoles
Chuangchuang Xu, Wenlai Xie, Jiaxi Xu Org Biomol Chem. 2020 Apr 8;18(14):2661-2671. doi: 10.1039/d0ob00317d.
A convenient, metal-free, and organic acid-base promoted synthetic method to prepare 3-arylindoles from 3-aryloxirane-2-carbonitriles and arylhydrazine hydrochlorides has been developed. In the reaction, the organic acid catalyzes a tandem nucleophilic ring-opening reaction of aryloxiranecarbonitriles and arylhydrazine hydrochlorides and Fischer indolization. The organic base triethylamine plays a crucial role in the final elimination step in the Fischer indole synthesis, affording 3-arylindoles regiospecifically. The reaction features advantages of microwave acceleration, non-metal participation, short reaction time, organic acid-base co-catalysis, and broad substrate scope.
