Small-molecule inhibitors of anthrax toxin / 国际药学研究杂志

Anthrax is a malignant infectious disease caused by Bacillus anthracis spores,after entering the host Bacillus an-thracis produces and releases anthrax toxin,which is the main cause leading to death of the host. The anthrax toxin is composed of two enzymatically active components:lethal factor(LF)and edema factor(EF),and one shared receptor binding and translocation com-ponent:protective antigen(PA). PA combined with LF is called lethal toxin(LeTx),while PA combined with EF called edema toxin (EdTx). Currently,the main drugs for treating anthrax are antibiotics,but antibiotics can only kill part of anthrax spores and bacte-ria,and cannot inhibit the activity of anthrax toxin. So it is necessary to develop novel drugs for inhibiting anthrax toxin. This review summarizes the evolution of small-molecule inhibitors of anthrax toxin respectively targeting PA,LF and EF.

BACE1 inhibitors:from peptide mimics to small molecules / 国际药学研究杂志

Alzheimer′s disease(AD)is a chronic neurodegenerative disorder. According to the amyloid cascade hypothesis, abnormal accumulation of amyloid peptides(Aβ)in the brain resulting in neuronal toxicity is the main cause of AD. β-secretase1 (BACE1)is a rate-limiting enzyme that hydrolyzesβ-amyloid precursor protein(β-APP)to produce amyloid peptides(Aβ). There?fore,BACE1 has been considered to be an attractive therapeutic target for the treatment of AD. Different structural classes of BACE 1 inhibitors have been designed and developed since BACE1 was cloned and identificated. This review highlights the core scaffold to summarize the evolution of structure-based design of BACE1 inhibitors.

Synthesis and preliminary analysis of the activity of N-benzyl-N-metylprop-2-yn-1-amine derivatives / 国际药学研究杂志

Objective To design and synthesize N-benzyl-N-metylprop-2-yn-1amine derivatives. Methods 3-methyl-benzoic acid was used as a raw material and we finish the synthesis through bromination,ammonolysis and condensation reaction. Time-resolved fluorescence was used to evaluate the inhibitory activity of these compounds againstβ-secretase. Results Three compounds were synthe-sized and the structures were confirmed by 1H NMR and LC-MS characterization. Conclusion The synthesized compounds have not been reported before and the synthetic route is reliable and easy to operate. The compounds have no obvious in hibitory effects againstβ-secre-tase.