Numao N, Hirota Y, Iwahori A, Kidokoro S, Sasatsu M, Kondo I, Itoh S, Itoh E, Katoh T, Shimozono N, Yamazaki A, Takao K, Kobayashi S
Sagami Chemical Research Center, Sagamihara, Kanagawa, Japan.
Biol Pharm Bull. 1999 Jan;22(1):73-6. doi: 10.1248/bpb.22.73.
MSI-78 is a peptide analog of naturally occurring magainin 2 isolated from the skin of Xenopus laevis. The peptide is known to have one of the strongest antibacterial activities in magainin 2 analogs against methicillin-resistant Staphylococcus aureus (MRSA). To find novel compounds superior to MSI-78, we have further designed, synthesizing 1,1-di(4-aminobutyl)-6-benzylindane (PM4) and 1,1-dibenzyl-6-(4-aminobutyl) indane (PM5), and tested their inhibitory ability of the growth of S. aureus. In an in vitro assay, PM4 showed the same antibacterial activity against the bacterium as MSI-78, and non-hemolytic activity against human red blood cells (RBCs) at the MIC (minimum inhibitory concentration) value, in contrast to the latter. On the other hand, PM5 showed stronger antibacterial activity than MSI-78, but being still accompanied with hemolysis at the MIC value. Otherwise, stronger decarboxylase activity for oxaloacetate was observed in PM5, rather than magainin 2 analogs or Oxaldie 1 as a control peptide, but not in PM4.
MSI-78是一种从非洲爪蟾皮肤中分离出的天然蛙皮素2的肽类似物。已知该肽在蛙皮素2类似物中对耐甲氧西林金黄色葡萄球菌（MRSA）具有最强的抗菌活性之一。为了找到优于MSI-78的新型化合物，我们进一步设计、合成了1,1-二（4-氨基丁基）-6-苄基茚满（PM4）和1,1-二苄基-6-（4-氨基丁基）茚满（PM5），并测试了它们对金黄色葡萄球菌生长的抑制能力。在体外试验中，PM4对该细菌显示出与MSI-78相同的抗菌活性，并且在MIC（最低抑菌浓度）值时对人红细胞（RBC）无溶血活性，这与MSI-78相反。另一方面，PM5显示出比MSI-78更强的抗菌活性，但在MIC值时仍伴有溶血现象。此外，与蛙皮素2类似物或作为对照肽的Oxaldie 1相比，在PM5中观察到更强的草酰乙酸脱羧酶活性，但在PM4中未观察到。
