Peptidoglycan N-acetylglucosamine (GlcNAc) deacetylases (PGNGdacs) from bacterial pathogens are validated targets for the development of novel antimicrobial agents. In this study we examined the in vitro inhibition of hydroxamate ligand N-hydroxy-4-(naphthalene-1-yl)benzamide (NHNB), a selective inhibitor of histone deacetylases-8 (HDAC8), against two PGNGdacs namely BC1974 and BC1960 from B. cereus, highly homologous to BA1977 and BA1961 of B. anthracis, respectively. Kinetic analysis showed that this compound functions as a competitive inhibitor of both enzymes with apparent K_i’s of 8.7 μM (for BC1974) and 66 μM (for BC1960), providing thus the most potent CE4 inhibitor reported to date. NHNB was tested in antibacterial assays and showed bactericidal activity against both examined pathogens acting as a multi-target drug. This compound can serve as lead for the development of inhibitors targeting the conserved active sites of the multiple polysaccharide deacetylases (PDAs) of both pathogens.

来自细菌病原体的肽聚糖N-乙酰氨基葡萄糖（GlcNAc）脱乙酰酶（PGNGdacs）是开发新型抗菌剂的有效靶标。在这项研究中，我们研究了异羟肟酸酯配体N-羟基-4-（萘-1-基）苯甲酰胺（NHNB）的体外抑制作用，它是组蛋白脱乙酰基酶8（HDAC8）的选择性抑制剂，针对两种PGNGdac，即BC1974和BC1960蜡状芽孢杆菌，分别与炭疽芽孢杆菌的BA1977和BA1961高度同源。动力学分析表明，该化合物作为两种酶的竞争性抑制剂，具有明显的K _i分别为8.7μM（对于BC1974）和66μM（对于BC1960），因此提供了迄今为止报道的最有效的CE4抑制剂。NHNB已通过抗菌测定进行了测试，显示出对两种被检验为多靶标药物的病原体的杀菌活性。该化合物可作为开发针对两种病原体的多种多糖脱乙酰酶（PDA）保守活性位点的抑制剂的先导。