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利用微生物衍生化合物的新治疗方法。

New therapeutic approaches by using microorganism-derived compounds.

机构信息

Viale Pieraccini 06, 50134 Florence, Italy.

出版信息

Curr Med Chem. 2012;19(22):3822-40. doi: 10.2174/092986712801661167.

Abstract

The role of natural products as a source for remedies has been recognized since ancient times. Despite major scientific and technological progress in combinatorial chemistry, drugs derived from natural product still make an enormous contribution to drug discovery today. Nature is an attractive source of new therapeutic candidate compounds since a tremendous chemical diversity is found in millions of species of plants, animals, marine organisms and microorganisms. Microorganisms such as bacteria and fungi have been invaluable to discover drugs and lead compounds. These microorganisms produce a large variety of antimicrobial agents which have evolved to give their hosts an advantage over their competitors in the microbiological world. The screening of microorganisms became highly popular after the discovery of penicillin but in recent years the list of antibacterial agents (bacteria- or fungi-derived) has increased considerably with the arrival of cephalosporins, tetracyclines, aminoglycosides, rifamycins, and chloramphenicol. Although most of the drugs derived from microorganisms are used in antibacterial therapy, some microbial metabolites have provided lead compounds in other fields of medicine. For example: the fungal metabolite lovastatin, which was the lead compound for a series of drugs that lower cholesterol levels, the ciclosporin (fungal metabolite) currently used to suppress the immune response after transplantation operations and sirolimus- a bacterium-derived macrolide- used in the treatment of some cancers. The aim of this review is to analyze the current uses and the future applications in therapeutic treatments of microorganism-derived products (MdPs) and discuss the results obtained in the some clinical trials.

摘要

天然产物作为药物来源的作用自古以来就已被认识。尽管在组合化学方面取得了重大的科学和技术进步,但今天从天然产物中获得的药物仍然为药物发现做出了巨大贡献。自然界是新治疗候选化合物的有吸引力的来源,因为在数以百万计的植物、动物、海洋生物和微生物物种中发现了巨大的化学多样性。微生物,如细菌和真菌,在发现药物和先导化合物方面发挥了巨大的作用。这些微生物产生了各种各样的抗菌剂,这些抗菌剂的进化是为了使其宿主在微生物世界中相对于其竞争者具有优势。自从青霉素被发现以来,微生物的筛选变得非常流行,但近年来,随着头孢菌素、四环素、氨基糖苷类、利福霉素和氯霉素的出现,抗菌药物(细菌或真菌来源)的清单大大增加。虽然大多数从微生物中获得的药物都用于抗菌治疗,但一些微生物代谢物已在医学的其他领域提供了先导化合物。例如:真菌代谢产物洛伐他汀,它是一系列降低胆固醇水平的药物的先导化合物;环孢菌素(真菌代谢物)目前用于抑制移植手术后的免疫反应;西罗莫司——一种细菌衍生的大环内酯类药物,用于治疗某些癌症。本文旨在分析微生物来源产品(MdPs)的当前用途和未来在治疗中的应用,并讨论一些临床试验中获得的结果。

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