University of Porto, Department of Chemistry and Biochemistry, REQUIMTE, Faculty of Sciences , Rua do Campo Alegre s/n, 4169-007 Porto , Portugal
Expert Opin Ther Pat. 2014 Aug;24(8):857-74. doi: 10.1517/13543776.2014.916280. Epub 2014 Jun 24.
In the recent decades, the interest on glycosidases has dramatically increased, mainly because these enzymes play a key role in many biological processes. The importance of these enzymes is also reflected by a number of diseases, which result from the lack or dysfunction of a given glycosidase, as well as by the use of glycosidase inhibitors in the treatment of metabolic disorders or viral infections. Based on the biological potential associated to these enzymes, several glycosidase inhibitors have been developed. In this review, the most important inhibitors targeting these enzymes, including the disaccharides, iminosugars, carbasugars, thiosugars and other non-glycosidic compounds will be discussed and special attention will be given to the ones that are currently used clinically.
This review summarizes and characterizes the current knowledge regarding the classes of glycosidase inhibitors that have therapeutic potential in a wide range of diseases. It highlights the relevant research, patents and patent applications filed in the past years on the field.
Since the glycosidase inhibitors are involved in several chronic diseases and possibly pandemic, the pharmaceutical research toward developing new generations of these molecules is very important to public health in the world. The unique combination of these compounds - for example, they share many properties with natural carbohydrates and also possess distinct specific characteristics - makes them precious for pharmaceutical companies in an attempt to search for potential new drugs. Currently, the most promising compounds are the iminosugars and thiosugars due to their better oral bioavailability.
近几十年来,糖苷酶的研究兴趣显著增加,主要是因为这些酶在许多生物过程中起着关键作用。这些酶的重要性还反映在许多疾病上,这些疾病要么是由于缺乏或功能失调的特定糖苷酶引起的,要么是由于使用糖苷酶抑制剂来治疗代谢紊乱或病毒感染。基于这些酶的生物学潜力,已经开发出了几种糖苷酶抑制剂。在这篇综述中,将讨论针对这些酶的最重要的抑制剂,包括二糖、亚氨基糖、碳环糖、硫代糖和其他非糖化合物,并特别关注目前临床上使用的抑制剂。
本综述总结并描述了具有广泛治疗潜力的糖苷酶抑制剂的种类,这些抑制剂在多种疾病中有应用价值。它突出了过去几年在该领域的相关研究、专利和专利申请。
由于糖苷酶抑制剂涉及多种慢性疾病,甚至可能涉及大流行疾病,因此针对这些分子开发新一代抑制剂的药物研究对全球公共卫生非常重要。这些化合物的独特组合——例如,它们与天然碳水化合物有许多共同特性,同时又具有独特的特定特征——使它们成为制药公司的宝贵资源,有助于寻找潜在的新药。目前,最有前途的化合物是亚氨基糖和硫代糖,因为它们具有更好的口服生物利用度。