Department of Organic Chemistry and BioTechMed Center, Gdańsk University of Technology, Gdańsk, Poland.
Department of Pharmaceutical Technology and Biochemistry and BioTechMed Center, Gdańsk University of Technology, Gdańsk, Poland.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1928-1956. doi: 10.1080/14756366.2022.2096018.
Glucosamine-6-phosphate synthase (GlcN-6-P synthase) is known as a promising target for antimicrobial agents and antidiabetics. Several compounds of natural or synthetic origin have been identified as inhibitors of this enzyme. This set comprises highly selective l-glutamine, amino sugar phosphate or transition state intermediate -enolamine analogues. Relatively low antimicrobial activity of these inhibitors, poorly penetrating microbial cell membranes, has been improved using the pro-drug approach. On the other hand, a number of heterocyclic and polycyclic compounds demonstrating antimicrobial activity have been presented as putative inhibitors of the enzyme, based on the results of molecular docking to GlcN-6-P synthase matrix. The most active compounds of this group could be considered promising leads for development of novel antimicrobial drugs or antidiabetics, provided their selective toxicity is confirmed.
葡萄糖胺-6-磷酸合酶（GlcN-6-P 合酶）是一种有前途的抗菌剂和抗糖尿病药物靶点。已经鉴定出几种天然或合成来源的化合物作为该酶的抑制剂。这些抑制剂包括高度选择性的 l-谷氨酰胺、氨基糖磷酸或过渡态中间物-烯醇胺类似物。这些抑制剂的抗菌活性相对较低，微生物细胞膜穿透性差，通过前药方法得到了改善。另一方面，根据分子对接 GlcN-6-P 合酶基质的结果，已经提出了许多具有抗菌活性的杂环和多环化合物作为该酶的假定抑制剂。如果证实其选择性毒性，该组中最有效的化合物可被认为是开发新型抗菌药物或抗糖尿病药物的有前途的先导化合物。
