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真菌细胞膜——抗真菌治疗中颇具前景的药物靶点。

Fungal cell membrane-promising drug target for antifungal therapy.

作者信息

Sant D G, Tupe S G, Ramana C V, Deshpande M V

机构信息

Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, India.

Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.

出版信息

J Appl Microbiol. 2016 Dec;121(6):1498-1510. doi: 10.1111/jam.13301. Epub 2016 Nov 2.

Abstract

Increase in invasive fungal infections over the past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armoury includes very few effective drugs like Amphotericin B; new generation azoles, including voriconazole and posaconazole; echinocandins like caspofungin and micafungin to name a few. Azole class of antifungals which target the fungal cell membrane are the first choice of treatment for many years because of their effectiveness. As the fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during the last few years. Present review focuses on cell membrane as an antifungal target with emphasis on membrane biogenesis, structure and function of cell membrane, cell membrane inhibitors, screening assays, recent advances and future prospects.

摘要

在过去几年中,侵袭性真菌感染有所增加,尤其是在免疫功能低下的患者中,这促使人们寻找疗效更佳的新型抗真菌药物。目前的抗真菌药物种类很少,如两性霉素B;新一代唑类药物,包括伏立康唑和泊沙康唑;棘白菌素类药物,如卡泊芬净和米卡芬净等等。由于其有效性,靶向真菌细胞膜的唑类抗真菌药物多年来一直是首选治疗药物。由于真菌细胞膜主要由甾醇、甘油磷脂和鞘脂组成,在过去几年中,研究人员在很大程度上致力于研究脂质在发病机制中的作用以及改善治疗的靶点识别。本综述聚焦于细胞膜作为抗真菌靶点,重点关注膜生物发生、细胞膜的结构和功能、细胞膜抑制剂、筛选试验、最新进展和未来前景。

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