Study on Interaction Between Boronic Acid and Hydroxyethylamines / 分析化学

The reversible covalent interaction between boronic acids and cis-diol-containing compounds provides unique affinity for recognition and separation of cis-diol-containing biomolecules such as glycoproteins and sugars. Herein, by using β-blockers and β-agonists as representative hydroxyethylamines, the interaction between phenylboronic acid and hydroxyethylamines was investigated through nuclear magnetic resonance ( NMR) and high performance liquid chromatography ( HPLC ) . The results showed that strong interaction between hydroxyethylamines and phenylboronic acid occurred at high pH value, while the interaction became much weaker and even disappeared at low pH value. This interaction was similar to boronate affinity interaction between boronic acids and cis-diol-containing compounds. However, unlike boronate affinity, the presence of an aprotic solvent disrupted the interaction. The above findings not only provided new insights for in-depth understanding boronate affinity interaction, but also paved the basis for the application of the interaction between boronic acid and hydroxyethylamines.

Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Design, synthesis and evaluation of novel hydroxyethylamine derivatives with nitrogen heterocyclic moiety at N-terminal as BACE1 inhibitors / 国际药学研究杂志

Objective: To develop a new series of hydroxy ethylamine (HEA) BACE1 inhibitors with nitrogen heterocyclic moiety at N-terminal and find new N-terminal moiety for enhancing BACE1 inhibition activity. Methods: New HEA compounds with nitrogen heterocyclic moiety at N-terminal were synthesized and evaluated as BACE1 inhibitors,with (-)-epigallocatechin-3-gallate EGCG as a positive control. Results: All new compounds were characterized by 1H NMR and ESI-MS. Evaluation of BACE1 inhibition activity showed that the compound I6 with indole moiety at N-terminal had BACE1 inhibition activity. Conclusion: The results suggested that the indole moiety at N-terminal interact with S2 pocket of BACE1 and be favorable for enhancing BACE1 inhibition activity, Thus, the indole moiety at N-terminal can be used as lead structure for further finding more effient BACE1 inhibitors.