![conference banner](/images/conference-banner.jpeg)
摘要
背景:COVID-19 在 60% 的国家扰乱了 NTD 项目,损害了公共卫生目标。因此,提高 NTD 的研究知识是一项艰巨的任务,并且候选人的体内筛选可以根据他们的整体情况提供有前途的选择。 目标:在这项工作中,我们强调了 2015-2021 年在合成和再利用药物领域所做的相关研究,这些药物在体内测试了南美锥虫病、疟疾和血吸虫病。 方法:使用 MEDLINE、PUBMED、CAPES PERIODIC 和 ELSEVIER 数据库对每个领域/疾病过去 6 年的研究进行全面的文献回顾。 结果:总体而言,研究集中在硝基杂环、芳香族硝基、核苷和金属基支架上,用于基于类似物的药物生成。重新利用被广泛评估,主要是杂环药物、它们的类似物,以及与当前治疗的组合。几个药物靶点针对南美锥虫治疗,具体的如铁超氧化物歧化酶,以及更一般的如线粒体功能障碍。对于疟疾,疟原虫色素仍然很受欢迎,而对于血吸虫病,更普遍的结构损伤和/或生殖障碍是针对作用机制的体外分析。 结论:最新的体内结果概述了每种疾病的趋势——对于恰加斯病,成功探索了杂环化合物作为噻唑;对于疟疾,喹啉衍生物仍然具有相关性,而对于血吸虫病,与合成化合物相比,来自不同类别的再利用药物表现出色。这项研究推动了南美锥虫病、疟疾和血吸虫病药物的持续发展,为研究人员提供了工具和信息来解决此类未满足的治疗需求。
关键词: 恰加斯病、血吸虫病、疟疾、动物筛查、合成化合物、再利用。
[http://dx.doi.org/10.1038/s41586-018-0327-4] [PMID: 30046073]
[http://dx.doi.org/10.3390/md16080279] [PMID: 30110923]
[http://dx.doi.org/10.3389/fmicb.2017.00717] [PMID: 28522990]
[http://dx.doi.org/10.1007/s00281-015-0538-9] [PMID: 26542392]
[http://dx.doi.org/10.1371/journal.pone.0002252] [PMID: 18493601]
[http://dx.doi.org/10.1016/j.chom.2015.02.011] [PMID: 25800544]
[http://dx.doi.org/10.2174/156802661815181101110430] [PMID: 30598060]
[http://dx.doi.org/10.2174/0929867327999201116145408] [PMID: 33198609]
[http://dx.doi.org/10.1126/science.aat0805] [PMID: 30655413]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00010]
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[http://dx.doi.org/10.1038/nrd.2018.92] [PMID: 29880920]
[http://dx.doi.org/10.1016/S0140-6736(17)31612-4] [PMID: 28673423]
[http://dx.doi.org/10.1128/AAC.03814-14] [PMID: 25512408]
[http://dx.doi.org/10.1016/j.ejmech.2015.06.018] [PMID: 26094151]
[http://dx.doi.org/10.1021/jm5015742] [PMID: 25580906]
[http://dx.doi.org/10.1016/j.bmc.2015.08.014] [PMID: 26344593]
[http://dx.doi.org/10.1016/j.ejmech.2016.08.002] [PMID: 27543881]
[http://dx.doi.org/10.1128/AAC.02717-16] [PMID: 28242662]
[http://dx.doi.org/10.1016/j.bmc.2015.10.048] [PMID: 26549870]
[http://dx.doi.org/10.1016/j.ejmech.2017.09.047] [PMID: 29031078]
[http://dx.doi.org/10.1016/j.ejmech.2014.11.004] [PMID: 25462275]
[http://dx.doi.org/10.1016/j.ejmech.2015.10.034] [PMID: 26523668]
[http://dx.doi.org/10.1016/j.exppara.2016.02.004] [PMID: 26874306]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00784]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00468] [PMID: 29883536]
[http://dx.doi.org/10.1016/j.bmc.2019.07.029] [PMID: 31345745]
[http://dx.doi.org/10.1016/j.micinf.2016.07.007] [PMID: 27484335]
[http://dx.doi.org/10.1128/AAC.01667-15] [PMID: 26856830]
[http://dx.doi.org/10.2147/DDDT.S120618] [PMID: 28435221]
[http://dx.doi.org/10.1128/AAC.02205-17] [PMID: 29203486]
[http://dx.doi.org/10.1016/j.ejmech.2017.08.055] [PMID: 28881289]
[http://dx.doi.org/10.1016/j.ejmech.2018.02.020] [PMID: 29501946]
[http://dx.doi.org/10.1016/j.biopha.2018.09.176] [PMID: 30372873]
[http://dx.doi.org/10.1002/cmdc.201800512] [PMID: 30098232]
[http://dx.doi.org/10.1128/AAC.01936-17] [PMID: 29203485]
[http://dx.doi.org/10.1016/j.ejmech.2019.111877] [PMID: 31771829]
[http://dx.doi.org/10.1021/acs.jmedchem.9b01275] [PMID: 31495177]
[http://dx.doi.org/10.1016/j.bmc.2020.115855] [PMID: 33199200]
[http://dx.doi.org/10.1016/j.exppara.2021.108125] [PMID: 34129877]
[http://dx.doi.org/10.3390/molecules26020423] [PMID: 33467422]
[http://dx.doi.org/10.1021/acsinfecdis.1c00048]
[http://dx.doi.org/10.1128/AAC.00520-15] [PMID: 26014936]
[http://dx.doi.org/10.1016/j.ijantimicag.2012.03.009] [PMID: 22591838]
[http://dx.doi.org/10.1371/journal.pone.0128707]
[http://dx.doi.org/10.1128/AAC.05785-11] [PMID: 22450981]
[http://dx.doi.org/10.1016/j.actatropica.2020.105606] [PMID: 32598923]
[http://dx.doi.org/10.1016/j.exppara.2018.04.016] [PMID: 29726395]
[PMID: 7568331]
[http://dx.doi.org/10.2174/1389557517666170315145410] [PMID: 28302040]
[http://dx.doi.org/10.1016/j.cbpa.2006.03.004] [PMID: 16626984]
[http://dx.doi.org/10.1371/journal.pntd.0007226] [PMID: 31536489]
[http://dx.doi.org/10.1371/journal.pntd.0002717] [PMID: 24587468]
[http://dx.doi.org/10.4269/ajtmh.15-0237] [PMID: 26350447]
[http://dx.doi.org/10.1016/j.exppara.2015.05.012] [PMID: 26183422]
[http://dx.doi.org/10.1038/cddis.2014.132] [PMID: 24763048]
[http://dx.doi.org/10.1016/j.bcp.2017.08.025]
[http://dx.doi.org/10.1039/C4OB02561J] [PMID: 25573664]
[http://dx.doi.org/10.1371/journal.pntd.0006764] [PMID: 30240395]
[http://dx.doi.org/10.1038/nrd2144] [PMID: 17080030]
[http://dx.doi.org/10.1128/AAC.02264-18] [PMID: 30962342]
[http://dx.doi.org/10.1016/S0140-6736(18)30324-6]
[http://dx.doi.org/10.1101/cshperspect.a025569]
[http://dx.doi.org/10.1016/j.bmcl.2015.04.014] [PMID: 25920564]
[http://dx.doi.org/10.3109/14756360903508430] [PMID: 20063996]
[http://dx.doi.org/10.1016/j.bmc.2015.06.056] [PMID: 26190461]
[http://dx.doi.org/10.1021/jm501809x] [PMID: 25654185]
[http://dx.doi.org/10.1016/j.bmc.2015.07.051] [PMID: 26264839]
[http://dx.doi.org/10.1016/j.ejmech.2016.06.033] [PMID: 27394399]
[http://dx.doi.org/10.1016/j.ijpddr.2018.10.002] [PMID: 30396013]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00143] [PMID: 29879353]
[http://dx.doi.org/10.1016/j.exppara.2018.01.015] [PMID: 29355497]
[http://dx.doi.org/10.1021/acsmedchemlett.8b00496] [PMID: 31097988]
[http://dx.doi.org/10.4103/0972-9062.289395] [PMID: 32655071]
[http://dx.doi.org/10.1186/s12936-015-1032-5] [PMID: 26671222]
[http://dx.doi.org/10.1016/j.bmc.2015.05.040] [PMID: 26081761]
[http://dx.doi.org/10.1021/acsomega.0c06053] [PMID: 34056449]
[http://dx.doi.org/10.1016/j.bmc.2021.116018] [PMID: 33524940]
[http://dx.doi.org/10.1038/s41421-020-00215-4] [PMID: 33311461]
[http://dx.doi.org/10.1021/acs.jmedchem.0c02104] [PMID: 33541085]
[http://dx.doi.org/10.1016/j.ejmech.2016.07.055] [PMID: 27494165]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00008] [PMID: 28537728]
[http://dx.doi.org/10.1016/j.ejmech.2017.04.022] [PMID: 28460309]
[http://dx.doi.org/10.1016/j.bmcl.2021.128305] [PMID: 34365007]
[http://dx.doi.org/10.1128/AAC.05012-14] [PMID: 25801563]
[http://dx.doi.org/10.3389/fcimb.2019.00009] [PMID: 30838177]
[http://dx.doi.org/10.1128/AAC.02005-16] [PMID: 27895022]
[http://dx.doi.org/10.1172/jci.insight.127441] [PMID: 31852843]
[http://dx.doi.org/10.1016/j.jddst.2020.102125]
[http://dx.doi.org/10.1016/j.biopha.2021.111275] [PMID: 33485067]
[http://dx.doi.org/10.1016/S1473-3099(16)30475-3] [PMID: 27988094]
[http://dx.doi.org/10.1016/j.actatropica.2016.06.024] [PMID: 27381578]
[http://dx.doi.org/10.1128/AAC.02582-16] [PMID: 28264841]
[http://dx.doi.org/10.1016/S2214-109X(17)30187-0] [PMID: 28619227]
[http://dx.doi.org/10.1007/s00436-012-3151-z] [PMID: 23052781]
[http://dx.doi.org/10.1016/j.ijpara.2016.03.006] [PMID: 27073078]
[http://dx.doi.org/10.1128/AAC.04463-14] [PMID: 25583726]
[http://dx.doi.org/10.1016/j.bmcl.2017.12.064] [PMID: 29317164]
[http://dx.doi.org/10.1039/C7MD00590C] [PMID: 30108926]
[http://dx.doi.org/10.1016/j.exppara.2020.107933] [PMID: 32525006]
[http://dx.doi.org/10.1016/j.ejps.2020.105236] [PMID: 32058057]
[http://dx.doi.org/10.1128/AAC.00778-16] [PMID: 27324765]
[http://dx.doi.org/10.1021/acsinfecdis.7b00054] [PMID: 28686009]
[http://dx.doi.org/10.1039/C8MD00396C] [PMID: 30568758]
[http://dx.doi.org/10.1016/j.ijpddr.2017.05.002] [PMID: 28511056]
[http://dx.doi.org/10.1007/s00436-018-6188-9] [PMID: 30617587]
[http://dx.doi.org/10.1186/s13071-019-3442-7] [PMID: 31053083]
[http://dx.doi.org/10.1371/journal.pntd.0003962] [PMID: 26230921]
[http://dx.doi.org/10.1186/s13071-015-1023-y] [PMID: 26265386]
[http://dx.doi.org/10.1016/j.actatropica.2014.12.005] [PMID: 25530543]
[http://dx.doi.org/10.1371/journal.pntd.0004928] [PMID: 27518281]
[http://dx.doi.org/10.1016/j.actatropica.2016.11.006] [PMID: 27836498]
[http://dx.doi.org/10.1128/AAC.01722-18] [PMID: 30559137]
[http://dx.doi.org/10.1128/AAC.01208-19] [PMID: 31527034]
[http://dx.doi.org/10.1016/j.ebiom.2019.04.029] [PMID: 31027918]
[http://dx.doi.org/10.1007/s00436-019-06259-0] [PMID: 30798369]
[http://dx.doi.org/10.1128/AAC.01372-20] [PMID: 32816737]
[http://dx.doi.org/10.1016/j.actatropica.2021.105891] [PMID: 33773944]
![Wayfinder Image](/images/wayfinder.jpg)