Numao N, Hirota Y, Iwahori A, Sasatsu M, Kondo I, Takao K, Kobayashi S
Sagami Chemical Research Center, Kanagawa, Japan.
Biol Pharm Bull. 1997 Nov;20(11):1204-7. doi: 10.1248/bpb.20.1204.
Magainin 2, isolated from the skin of the Xenopus laevis, is an antimicrobial peptide which reacts directly with the biological membrane to lyse various bacteria from negative and positive microorganisms. In a previous report, we showed that (+/-)1-(4-aminobutyl)-6-benzylindane (PM2), which mimicked the conformation of the side-chains of a complementary unit on the amino acid sequence of magainin 2 analogs, expressed the in vitro antibacterial activity not only against Helicobacter, pylori (ATCC43526, ATCC43579), but also against Escherichia coli (ATCC25922) and Staphylococcus aureus (ATCC25923). In addition, PM2 caused human blood red cells (RBCs) to lyse at the minimum inhibitory concentration (MIC) value. Based on the antibacterial activities of 9-phenylnonanoic acid (pC9c), we further synthesized (+/-)-6-benzyl-1-(3-carboxypropyl) indane (PM2c), which replaced a positive charge of PM2 with a negative one, and tested the biological activities. PM2c had the ability to inhibit the growth of H. pylori strains, but its activity to inhibit the growth of E. coli and S. aureus was not detected and weak, respectively. Moreover, PM2c showed non-hemolytic activity against RBCs at the MIC value. These results indicate the possibility that PM2c may be more useful than PM2 either alone or in combination with well-known therapeutic agents for the treatment of H. pylori infection.
爪蟾抗菌肽2是从非洲爪蟾皮肤中分离出来的一种抗菌肽，它能直接与生物膜发生反应，裂解各种阴性和阳性微生物中的细菌。在之前的一份报告中，我们表明，（±）-1-（4-氨基丁基）-6-苄基茚满（PM2）模拟了爪蟾抗菌肽2类似物氨基酸序列上互补单元侧链的构象，不仅对幽门螺杆菌（ATCC43526、ATCC43579）具有体外抗菌活性，而且对大肠杆菌（ATCC25922）和金黄色葡萄球菌（ATCC25923）也有活性。此外，PM2在最低抑菌浓度（MIC）值时会导致人血红细胞（RBC）裂解。基于9-苯基壬酸（pC9c）的抗菌活性，我们进一步合成了（±）-6-苄基-1-（3-羧丙基）茚满（PM2c），它将PM2的正电荷替换为负电荷，并测试了其生物活性。PM2c有抑制幽门螺杆菌菌株生长的能力，但未检测到其对大肠杆菌和金黄色葡萄球菌的抑制活性，且抑制活性较弱。此外，PM2c在MIC值时对RBC表现出非溶血活性。这些结果表明，PM2c单独或与知名治疗药物联合使用治疗幽门螺杆菌感染可能比PM2更有用。
