Claesson A, Jansson A M, Pring B G, Hammond S M, Ekström B
Department of Antibacterial Chemotherapy, Research and Development, Astra Alab, Södertälje, Sweden.
J Med Chem. 1987 Dec;30(12):2309-13. doi: 10.1021/jm00395a022.
On the basis of the knowledge that the amino acid 3 (8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid) is a potent inhibitor of 3-deoxy-manno-octulosonate cytidylyltransferase, attempts were made to design derivatives that would act as antibacterials against Gram-negative bacteria by inhibiting lipopolysaccharide biosynthesis. Compound 3 and the derivatives 15 and 16 containing an additional amino acid were not lethal to bacteria. However, compounds 17-22, which contain a N-terminally linked dipeptide, exhibited good antibacterial activity in vitro on testing against strains of the Gram-negative bacteria Escherichia coli and Salmonella typhimurium. They have no activity against Gram-positive bacteria such as Staphylococcus aureus.
基于氨基酸3（8-氨基-2,6-脱水-3,8-二脱氧-D-甘油-D-塔罗辛酸）是3-脱氧-D-甘露糖辛酸胞苷转移酶的有效抑制剂这一知识，人们尝试设计通过抑制脂多糖生物合成来对抗革兰氏阴性菌的衍生物。化合物3以及含有额外氨基酸的衍生物15和16对细菌没有致死性。然而，含有N端连接二肽的化合物17 - 22在体外对革兰氏阴性菌大肠杆菌和鼠伤寒沙门氏菌菌株进行测试时表现出良好的抗菌活性。它们对革兰氏阳性菌如金黄色葡萄球菌没有活性。
