Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer ce...Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure–activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.展开更多
Infection with hepatitis C virus(HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care(SOC) involv...Infection with hepatitis C virus(HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care(SOC) involving pegylated interferon-α(PEG-IFN α) plus ribavirin(RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1,the most prevalent type of HCV in North America and Europe.Recently,reliable in vitro culture systems have been developed for accelerating antiviral therapy research,and many new specifically targeted antiviral therapies for hepatitis C(STAT-C) and treatment strategies are being evaluated in clinical trials.These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration.The aim of this review is to summarize the current developments in new anti-HCV drugs.展开更多
背景:H型血管是近年来新发现的一种能够偶联成血管和成骨两种生理过程的特殊血管亚型,在骨骼系统的生理及病理过程中均扮演重要角色。天然小分子化合物具有来源广泛、毒副反应低等优点。近年来研究发现天然小分子化合物对H型血管也具有...背景:H型血管是近年来新发现的一种能够偶联成血管和成骨两种生理过程的特殊血管亚型,在骨骼系统的生理及病理过程中均扮演重要角色。天然小分子化合物具有来源广泛、毒副反应低等优点。近年来研究发现天然小分子化合物对H型血管也具有调控作用。目的:总结H型血管的基本特征,并讨论几种天然小分子化合物在治疗骨相关疾病治疗中的应用现状及前景。方法:在Web of Science、PubMed、中国知网和万方数据库中,以“H型血管、天然小分子化合物、天然小分子药物、中药活性成分”为中文检索词,以“type H vessel,H-type vessel,type H microvessel,type H blood vessel,CD31hiEmcnhiendothelial cell,CD31hiEndomucinhibloodvessel,CD31^((hi))Emcn^((hi))endothelialcell,specific vessel subtype,natural small molecular compounds,Chinesemedicine,Chinese traditional medicine,Chinese plant extracts”为英文检索词进行文献检索。检索时间范围为2014年1月至2022年6月。通过阅读文题和摘要进行初步筛选,排除中英文文献重复性研究及内容不相关的文献,经文献质量评价后,最后纳入65篇文献进行综述。结果与结论:(1)H型血管是一种特殊血管亚型,主要分布于长骨干骺端及骨内膜处,在扁骨与不规则骨中也有分布,且在多数部位,有典型的柱状或栅栏状排列结构;H型血管的长度及数量在不同部位均呈现年龄相关性。(2)H型血管在偶联成骨-成血管两种生理过程中起到重要作用,其可以通过血管旁分泌的作用对成骨系和破骨系细胞发挥募集与调节作用。(3)H型血管在骨疾病的发生发展中扮演重要角色,多种天然小分子化合物在通过调控H型血管治疗骨关节炎、骨质疏松、骨折和去负荷性骨丢失等疾病中具有较好效果;例如三七的提取物邻苯二甲酸二叔丁酯可以抑制异常的H型血管生成,以缓解骨关节炎病情进展,人参的提取物人参皂甙化合物K可以促进愈伤组织中H型血管生成,加快骨折愈合。(4)鉴于组织工程支架负载药物及细胞因子调控H型血管治疗骨疾病以及天然小分子化合物在调控H型血管所体现出的较好效果,将组织工程支架与天然小分子化合物结合调控H型血管显示出良好的前景。展开更多
以5-溴水杨醛、4-氯苄氯为原料,通过消去、还原及溴化合成了4-溴-2-溴甲基-1-((4-溴苄基)氧)苯(3),以哌啶-4-酮合成了N-烯丙基-N-(4-哌啶基)对氯苯甲酰胺(7),通过(3)、(7)合成了一种新的非肽类小分子化合物CCR5拮抗剂N-烯丙基-N-(1-(5-...以5-溴水杨醛、4-氯苄氯为原料,通过消去、还原及溴化合成了4-溴-2-溴甲基-1-((4-溴苄基)氧)苯(3),以哌啶-4-酮合成了N-烯丙基-N-(4-哌啶基)对氯苯甲酰胺(7),通过(3)、(7)合成了一种新的非肽类小分子化合物CCR5拮抗剂N-烯丙基-N-(1-(5-溴-2-((4-氯苄基)氧基)苄基)-4-哌啶基)-4-氯苯甲酰胺(8),并对该产物进行了1 H NMR、13C NMR及MS表征。展开更多
以1-苯甲基-4-哌啶酮合成了4-甲基-N-乙基-N-(4-哌啶基)苯磺酰胺(中间体7),以4-氯苯甲氯为原料,通过溴化及还原合成了5-溴-2-(4-氯苯甲氧基)溴甲基苯(中间体3),通过中间体7和中间体3合成了一种新的小分子化合物4-甲基-N-乙基-N-(N-(5-溴...以1-苯甲基-4-哌啶酮合成了4-甲基-N-乙基-N-(4-哌啶基)苯磺酰胺(中间体7),以4-氯苯甲氯为原料,通过溴化及还原合成了5-溴-2-(4-氯苯甲氧基)溴甲基苯(中间体3),通过中间体7和中间体3合成了一种新的小分子化合物4-甲基-N-乙基-N-(N-(5-溴-2-(4-氯苯甲基氧基)苯甲基)-4-哌啶基)苯磺酰胺,对该产物进行了1 H NMR、MS、IR表征及生物活性检测,结果表明该化合物可以作为药物开发的候选化合物.展开更多
文摘Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure–activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.
基金Project partially supported by the Centers for Oceans and Human Health Program of the National Institute of Environmental Health Sciences (No.P50ES012740)the National Science Foundation of USA (Nos.OCE04-32479 and OCE09-11000)the National Mega Project on Major Drug Development of China (No.2011ZX09401-302)
文摘Infection with hepatitis C virus(HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care(SOC) involving pegylated interferon-α(PEG-IFN α) plus ribavirin(RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1,the most prevalent type of HCV in North America and Europe.Recently,reliable in vitro culture systems have been developed for accelerating antiviral therapy research,and many new specifically targeted antiviral therapies for hepatitis C(STAT-C) and treatment strategies are being evaluated in clinical trials.These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration.The aim of this review is to summarize the current developments in new anti-HCV drugs.
文摘背景:H型血管是近年来新发现的一种能够偶联成血管和成骨两种生理过程的特殊血管亚型,在骨骼系统的生理及病理过程中均扮演重要角色。天然小分子化合物具有来源广泛、毒副反应低等优点。近年来研究发现天然小分子化合物对H型血管也具有调控作用。目的:总结H型血管的基本特征,并讨论几种天然小分子化合物在治疗骨相关疾病治疗中的应用现状及前景。方法:在Web of Science、PubMed、中国知网和万方数据库中,以“H型血管、天然小分子化合物、天然小分子药物、中药活性成分”为中文检索词,以“type H vessel,H-type vessel,type H microvessel,type H blood vessel,CD31hiEmcnhiendothelial cell,CD31hiEndomucinhibloodvessel,CD31^((hi))Emcn^((hi))endothelialcell,specific vessel subtype,natural small molecular compounds,Chinesemedicine,Chinese traditional medicine,Chinese plant extracts”为英文检索词进行文献检索。检索时间范围为2014年1月至2022年6月。通过阅读文题和摘要进行初步筛选,排除中英文文献重复性研究及内容不相关的文献,经文献质量评价后,最后纳入65篇文献进行综述。结果与结论:(1)H型血管是一种特殊血管亚型,主要分布于长骨干骺端及骨内膜处,在扁骨与不规则骨中也有分布,且在多数部位,有典型的柱状或栅栏状排列结构;H型血管的长度及数量在不同部位均呈现年龄相关性。(2)H型血管在偶联成骨-成血管两种生理过程中起到重要作用,其可以通过血管旁分泌的作用对成骨系和破骨系细胞发挥募集与调节作用。(3)H型血管在骨疾病的发生发展中扮演重要角色,多种天然小分子化合物在通过调控H型血管治疗骨关节炎、骨质疏松、骨折和去负荷性骨丢失等疾病中具有较好效果;例如三七的提取物邻苯二甲酸二叔丁酯可以抑制异常的H型血管生成,以缓解骨关节炎病情进展,人参的提取物人参皂甙化合物K可以促进愈伤组织中H型血管生成,加快骨折愈合。(4)鉴于组织工程支架负载药物及细胞因子调控H型血管治疗骨疾病以及天然小分子化合物在调控H型血管所体现出的较好效果,将组织工程支架与天然小分子化合物结合调控H型血管显示出良好的前景。
文摘以5-溴水杨醛、4-氯苄氯为原料,通过消去、还原及溴化合成了4-溴-2-溴甲基-1-((4-溴苄基)氧)苯(3),以哌啶-4-酮合成了N-烯丙基-N-(4-哌啶基)对氯苯甲酰胺(7),通过(3)、(7)合成了一种新的非肽类小分子化合物CCR5拮抗剂N-烯丙基-N-(1-(5-溴-2-((4-氯苄基)氧基)苄基)-4-哌啶基)-4-氯苯甲酰胺(8),并对该产物进行了1 H NMR、13C NMR及MS表征。
文摘以1-苯甲基-4-哌啶酮合成了4-甲基-N-乙基-N-(4-哌啶基)苯磺酰胺(中间体7),以4-氯苯甲氯为原料,通过溴化及还原合成了5-溴-2-(4-氯苯甲氧基)溴甲基苯(中间体3),通过中间体7和中间体3合成了一种新的小分子化合物4-甲基-N-乙基-N-(N-(5-溴-2-(4-氯苯甲基氧基)苯甲基)-4-哌啶基)苯磺酰胺,对该产物进行了1 H NMR、MS、IR表征及生物活性检测,结果表明该化合物可以作为药物开发的候选化合物.
文摘目的高通量筛选技术筛选抑制肝癌(PLC)细胞生长的新型小分子化合物。方法将PLC HepG2、Huh7细胞进行培养,培养后用于实验。选择3个小分子化合物数据库(合计3272个小分子化合物),分别为Prestwick、Tocriscreen、Selleck Chem。以及进行高通量筛选和靶化合物的筛选。结果本研究从3272个小分子化合物中利用高通量筛选技术选出抑制PLC细胞生长的目的化合物(hits)。初筛出的hits为z-score<-1.5,差异有统计学意义( P <0.05)。本研究通过比较9块化合物筛选板2种PLC细胞系(HepG2、Huh7)的重叠区域,共筛选出31种能够同时抑制这2个细胞系生长,且z-score<-1.5的化合物。最终筛选出36种hits化合物,包括5种临床治疗PLC的常用化疗药物和分子式。阿霉素作为hits被2次筛选出来,故最终初筛成功的新型化合物共有31种。结论通过高通量筛选技术筛选出31种可能具有抑制PLC细胞生长作用的新型小分子化合物,且有可能成为PLC治疗中的新型靶向药物。
