There are two new trends in the development of novel Pharmaceuticals. Biotechnology provides a novel approach to rational drug design. At the same time, there has been a growing interest in the use of herbal products....There are two new trends in the development of novel Pharmaceuticals. Biotechnology provides a novel approach to rational drug design. At the same time, there has been a growing interest in the use of herbal products. Chinese medical herbs are rich in the natural resources and have been used for thousands years in China. We consider the Chinese medicine system as a natural combinatorial chemi-展开更多
Alzheimer’s disease(AD)is the most common age-dependent neurodegenerative disease which impairs cognitive function and gradually causes patients to be unable to lead normal daily lives.While the etiology of AD remain...Alzheimer’s disease(AD)is the most common age-dependent neurodegenerative disease which impairs cognitive function and gradually causes patients to be unable to lead normal daily lives.While the etiology of AD remains an enigma,excessive accumulation ofβ-amyloid peptide(Aβ)is widely believed to induce pathological changes and cause dementia in brains of AD patients.BACE1 was discovered to initiate the cleavage of amyloid precursor protein(APP)at theβ-secretase site.Only after this cleavage doesγ-secretase further cleave the BACE1-cleaved C-terminal APP fragment to release Aβ.Hence,blocking BACE1 proteolytic activity will suppress Aβgeneration.Due to the linkage of Aβto the potential cause of AD,extensive discovery and development efforts have been directed towards potent BACE1 inhibitors for AD therapy.With the recent breakthrough in developing brain-penetrable BACE1 inhibitors,targeting amyloid deposition-mediated pathology for AD therapy has now become more practical.This review will summarize various strategies that have successfully led to the discovery of BACE1 drugs,such as MK8931,AZD-3293,JNJ-54861911,E2609 and CNP520.These drugs are currently in clinical trials and their updated states will be discussed.With the promise of reducing Aβgeneration and deposition with no alarming safety concerns,the amyloid cascade hypothesis in AD therapy may finally become validated.展开更多
A new series of multi-heterocyclic Schiff base was constructed starting from 4＇-（imidazol-1-yl[56_TD$IF]）-acetophenone which was converted to its 2-bromoethanone precursor which on cyclic condensation with thiourea...A new series of multi-heterocyclic Schiff base was constructed starting from 4＇-（imidazol-1-yl[56_TD$IF]）-acetophenone which was converted to its 2-bromoethanone precursor which on cyclic condensation with thiourea yielded final thiazol-2-amine intermediate（3） to be reacted with substituted aldehydes to generate final imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines（4a–4i）. New Schiff base was investigated for their in vitro cytotoxic efficacies against a panel of three human cancer cell lines namely, MCF7（human breast cancer）, HCT116（human colon cancer）, and DU145（human prostate cancer） and one normal skin fibroblast（SF）. Most of these synthetic derivatives shown important cytotoxic actions against individual carcinoma cell line collections, but weak actions against SF, which is as anticipated. Observations of SAR suggested that the difference in the characteristics of substituents attached to the Schiff base function leads to the interesting variations within pharmacological effects of resultant molecular systems. Structural analysis performed using FT-IR,~1H NMR,^（13）C NMR spectroscopy and CHN analysis for final potent anticancer Schiff base, which warrant further investigations.展开更多
Objective To investigate the current conditions of the main chronic diseases and to make the control policy in community health management base in China. MethodsThe questionnaire consisting of prevalence, awareness ra...Objective To investigate the current conditions of the main chronic diseases and to make the control policy in community health management base in China. MethodsThe questionnaire consisting of prevalence, awareness rate, management rate, behavior correct rate, control rate, and medicine obey was used to survey the chronic disease condition in 2009. A total of 809 736 residents were randomly selected from Shanghai and Guangdong, China. ResultsThe hypertension prevalence was 17.81%. From sex analysis, the female has higher rate than male in hypertension prevalence, understand rate, management rate, behavior correct rate, control rate, and medicine obey rate. From age analysis, the prevalence, understand rate, management rate, control rate, and medicine obey were increasing along with the age, but behavior correct rate was not in this condition. The diabetes prevalence was 6.92%. To compare with Shanghai and Guangzhou in 5 aspects, the prevalence of chronic diseases was alike. Except lower behavior correct rate in Shanghai, management rate, behavior correct rate, control rate, and medicine obey rate were higher in Shanghai. ConclusionThe government must take main principle in chronic disease control. Base construction of community health management and increase management level of chronic diseases should be enhanced and practitioner's knowledge of chronic disease management should also be enhanced.展开更多
文摘There are two new trends in the development of novel Pharmaceuticals. Biotechnology provides a novel approach to rational drug design. At the same time, there has been a growing interest in the use of herbal products. Chinese medical herbs are rich in the natural resources and have been used for thousands years in China. We consider the Chinese medicine system as a natural combinatorial chemi-
基金R Yan is supported by the grant(AG025493,MH103942,NS074256 and AG046929)from the National Institutes of Health.
文摘Alzheimer’s disease(AD)is the most common age-dependent neurodegenerative disease which impairs cognitive function and gradually causes patients to be unable to lead normal daily lives.While the etiology of AD remains an enigma,excessive accumulation ofβ-amyloid peptide(Aβ)is widely believed to induce pathological changes and cause dementia in brains of AD patients.BACE1 was discovered to initiate the cleavage of amyloid precursor protein(APP)at theβ-secretase site.Only after this cleavage doesγ-secretase further cleave the BACE1-cleaved C-terminal APP fragment to release Aβ.Hence,blocking BACE1 proteolytic activity will suppress Aβgeneration.Due to the linkage of Aβto the potential cause of AD,extensive discovery and development efforts have been directed towards potent BACE1 inhibitors for AD therapy.With the recent breakthrough in developing brain-penetrable BACE1 inhibitors,targeting amyloid deposition-mediated pathology for AD therapy has now become more practical.This review will summarize various strategies that have successfully led to the discovery of BACE1 drugs,such as MK8931,AZD-3293,JNJ-54861911,E2609 and CNP520.These drugs are currently in clinical trials and their updated states will be discussed.With the promise of reducing Aβgeneration and deposition with no alarming safety concerns,the amyloid cascade hypothesis in AD therapy may finally become validated.
基金supported by Dongguk University-Seoul,Republic of Korea,research funds 2016-2017supported by the KU Research Professor Program of Konkuk University, Seoul, Republic of Korea
文摘A new series of multi-heterocyclic Schiff base was constructed starting from 4＇-（imidazol-1-yl[56_TD$IF]）-acetophenone which was converted to its 2-bromoethanone precursor which on cyclic condensation with thiourea yielded final thiazol-2-amine intermediate（3） to be reacted with substituted aldehydes to generate final imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines（4a–4i）. New Schiff base was investigated for their in vitro cytotoxic efficacies against a panel of three human cancer cell lines namely, MCF7（human breast cancer）, HCT116（human colon cancer）, and DU145（human prostate cancer） and one normal skin fibroblast（SF）. Most of these synthetic derivatives shown important cytotoxic actions against individual carcinoma cell line collections, but weak actions against SF, which is as anticipated. Observations of SAR suggested that the difference in the characteristics of substituents attached to the Schiff base function leads to the interesting variations within pharmacological effects of resultant molecular systems. Structural analysis performed using FT-IR,~1H NMR,^（13）C NMR spectroscopy and CHN analysis for final potent anticancer Schiff base, which warrant further investigations.
文摘Objective To investigate the current conditions of the main chronic diseases and to make the control policy in community health management base in China. MethodsThe questionnaire consisting of prevalence, awareness rate, management rate, behavior correct rate, control rate, and medicine obey was used to survey the chronic disease condition in 2009. A total of 809 736 residents were randomly selected from Shanghai and Guangdong, China. ResultsThe hypertension prevalence was 17.81%. From sex analysis, the female has higher rate than male in hypertension prevalence, understand rate, management rate, behavior correct rate, control rate, and medicine obey rate. From age analysis, the prevalence, understand rate, management rate, control rate, and medicine obey were increasing along with the age, but behavior correct rate was not in this condition. The diabetes prevalence was 6.92%. To compare with Shanghai and Guangzhou in 5 aspects, the prevalence of chronic diseases was alike. Except lower behavior correct rate in Shanghai, management rate, behavior correct rate, control rate, and medicine obey rate were higher in Shanghai. ConclusionThe government must take main principle in chronic disease control. Base construction of community health management and increase management level of chronic diseases should be enhanced and practitioner's knowledge of chronic disease management should also be enhanced.
