Abstract

A new diketopiperazine, cyclo-( d -8-acetoxyl-Pro- l -Leu) (1), together with eight known compounds (2–9) including three enterotoxins (2–4), four diketopiperazines (5–8) and maltol (9), were isolated from the mangrove derived-soil Streptomyces sp. SCSIO 41400. The planar structures of all compounds were determined from analysis of NMR spectra, MS, optical rotation and comparing with literature data. The absolute configuration of compound 1 was assigned by electronic circular dichroism (ECD). The isolated compounds (1–9) were tested for their acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Among them, the new diketopiperazine (1) displayed preferable PL enzyme inhibitory activity with IC₅₀ value of 27.3 μg/mL, while compounds 2, 5 and 6 showed weak PL enzyme inhibitory activity. Further molecular docking simulation exhibited that compound 1 could be well bind with the catalytic pocket of the PL. Besides, compound 9 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, which was comparable to that of the positive control ampicillin with MIC value of 3.125 μg/mL.

摘要

一种新的二酮哌嗪环-( d -8-acetoxyl-Pro- l - Leu ) ( 1 )，连同八种已知化合物 ( 2-9 ) ，包括三种肠毒素 ( 2-4 )、四种二酮哌嗪( 5-8 )和麦芽酚 ( 9 ) 是从红树林衍生的土壤链霉菌中分离得到的。SCIO 41400。所有化合物的平面结构均通过分析核磁共振光谱、质谱、旋光度并与文献数据进行比较来确定。化合物1的绝对构型由电子圆二色谱 (ECD) 指定。分离的化合物 ( 1 – 9 ) 对其乙酰胆碱酯酶 (AChE) 和胰脂肪酶 (PL) 酶抑制活性进行了测试。其中，新型二酮哌嗪( 1 )表现出较好的PL酶抑制活性，IC 50_值为27.3 μg/mL，而化合物2、5、6表现出较弱的PL酶抑制活性。进一步的分子对接模拟表明，化合物1可以很好地与 PL 的催化口袋结合。此外，化合物9对耐甲氧西林金黄色葡萄球菌具有中等抗菌活性。MIC值为12.5 μg/mL，与MIC值为3.125 μg/mL的阳性对照氨苄西林相当。