摘要
传染病是世界上最重要和紧迫的健康问题之一。根据世界卫生组织(WHO)统计,传染病和寄生虫病是全世界约16%的死亡病例,非洲死亡人数超过40%。近一百年来在传染病,特别是细菌感染的斗争中取得的长足进步主要归因于三个因素:(1)生活条件,特别是卫生条件的普遍改善; (2)开发疫苗和(3)开发有效的抗菌药物。虽然减少细菌感染病例数量,特别是致死性病例数量有了长足的进步,但这些疾病的继续病例和疫情持续存在,这是由不同的因素造成的。事实上,过去六十年来,抗菌药物被用来抵抗由细菌病原体引起的各种感染性疾病,取得了无可比拟的成功。抗生素发展最有成果的时期持续到上世纪40年代至60年代,导致目前市场上大多数抗生素通过筛选来自土壤的放线菌获得。虽然抗菌药物市场今年每年超过250亿美元,但由于许多致病菌对目前的抗生素产生耐药性,仍然需要新的抗菌药物。在过去五年中,人们可以观察到致力于治疗肺炎和泌尿道感染的抗性细菌菌株(例如肺炎克雷伯杆菌和大肠杆菌)的急剧增加。耐药细菌菌株的发展是抗生素应用于治疗的副作用:由于存在抗生素耐受性持久性,感染变得不可治愈。 在这次审查中,我们讨论了抗菌药物发现的挑战,包括抗药性的分子基础,新型抗菌药物的药物靶标和新化合物(自2010年起),从具有抗菌活性的不同化学类别,重点关注结构 - 活性关系。
关键词: 抗菌活性,抗菌化合物,抗菌药物靶标,抗生素耐药性,传染病治疗,结构活性关系
Current Medicinal Chemistry
Title:Novel Antibacterial Compounds and their Drug Targets - Successes and Challenges
Volume: 24 Issue: 18
关键词: 抗菌活性,抗菌化合物,抗菌药物靶标,抗生素耐药性,传染病治疗,结构活性关系
摘要: Infectious diseases are one of the most important and urgent health problems in the world. According to the World Health Organization (WHO) statistics, infectious and parasitic diseases are a cause of about 16% of all deaths worldwide and over 40% of deaths in Africa. A considerable progress that has been made during last hundred years in the fight against infectious diseases, in particular bacterial infections, can be attributed mainly to three factors: (1) the general improvement of living conditions, in particular sanitation; (2) development of vaccines and (3) development of efficient antibacterial drugs. Although considerable progress in reduction of the number of cases of bacterial infections, especially in lethal cases, has been made, continued cases and outbreaks of these diseases persist, which is caused by different contributing factors. Indeed, during last sixty years antibacterial drugs were used against various infectious diseases caused by bacterial pathogens with an undoubtable success. The most fruitful period for antibiotic development lasted from 40’s to 60’s of the last century and resulted in the majority of antibiotics currently on the market, which were obtained by screening actinomycetes derived from soil. Although the market for antibacterial drugs is nowadays greater than 25 billion US dollars per year, novel antibacterial drugs are still demanded due to developed resistance of many pathogenic bacteria against current antibiotics. In the last five years, one can observe a dramatic increase in cases of resistant bacteria strains (e.g. Klebsiella pneumoniae and E. coli) which are responsible for difficult to treat pneumonia and infections of urinary tract. The development of resistant bacteria strains is a side effect of antibiotic application for treatment: the infections become untreatable as a result of the existence of antibiotic-tolerant persisters.
In this review, we discuss the challenges in antibacterial drug discovery, including the molecular basis of drug resistance, drug targets for novel antibacterial drugs, and new compounds (since year 2010) from different chemical classes with antibacterial activity, focusing on structure-activity relationships.Export Options
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Cite this article as:
Novel Antibacterial Compounds and their Drug Targets - Successes and Challenges, Current Medicinal Chemistry 2017; 24 (18) . https://dx.doi.org/10.2174/0929867323666161213102127
DOI https://dx.doi.org/10.2174/0929867323666161213102127 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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