Faculty of Medicine and Health Technology, University of Tampere, 33014 Tampere, Finland.
Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS, ENSCM, Université de Montpellier, 34296 Montpellier CEDEX 05, France.
Molecules. 2018 Nov 8;23(11):2911. doi: 10.3390/molecules23112911.
Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three β-CAs that have been cloned and characterized from (Mtb) and the crystal structures of two of the enzymes have been determined. Different classes of inhibitor molecules against Mtb β-CAs have subsequently been designed and have been shown to inhibit these mycobacterial enzymes . The inhibition of these centrally important mycobacterial enzymes leads to reduced growth of mycobacteria, lower virulence, and impaired biofilm formation. Thus, the inhibition of β-CAs could be a novel approach for developing drugs against the severe diseases caused by pathogenic mycobacteria. In the present article, we review the data related to and inhibition studies in the field.
分枝杆菌可引起多种疾病,如结核病、麻风病和免疫功能低下者的机会性疾病。这些疾病的治疗存在问题,需要开发新的治疗策略。最近,β-碳酸酐酶(β-CAs)已成为分枝杆菌中的潜在药物靶点。分枝杆菌的基因组编码三种β-CAs,已从结核分枝杆菌(Mtb)中克隆和鉴定,并已确定两种酶的晶体结构。随后设计了不同类别的抑制分子来抑制 Mtbβ-CAs,并已证明这些抑制分子可抑制这些分枝杆菌酶。这些对中心重要的分枝杆菌酶的抑制导致分枝杆菌的生长减少、毒力降低和生物膜形成受损。因此,抑制β-CAs 可能是开发针对致病性分枝杆菌引起的严重疾病的药物的新方法。在本文中,我们综述了该领域与 Mtbβ-CAs 抑制研究相关的数据。