Abstract

A new indole diketopiperazine alkaloid, named penilline D (1), together with five known indole alkaloid analogues (2–5, 11), two meroterpenoids (6 and 12), and four butenolide derivatives (7–10), were isolated from the Antarctic fungus Penicillium sp. SCSIO 05705. Extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation were used to elucidate the structure of penilline D (1), including its absolute configuration. All isolated compounds (1–12) were evaluated for their cytotoxic, antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among them, compound 5 exhibited moderate in vitro cytotoxic activity against the 143B cell line with IC₅₀ value of 12.64 ± 0.78 μM. Compound 6 showed strong inhibitory activity against AChE with IC₅₀ value of 0.36 nM (IC₅₀ 18.7 nM for Tacrine), while compounds 6 and 11 showed weak PL enzyme inhibitory activity. Furthermore, an in silico molecular docking study was also performed between 6 and AChE.

摘要

一种新的吲哚二酮哌嗪生物碱，命名为 penilline D ( 1 )，连同五种已知的吲哚生物碱类似物 ( 2 – 5 , 11 )、两种类萜 ( 6和12 ) 和四种丁烯内酯衍生物 ( 7 – 10 )，从南极真菌Penicillium sp. SCSIO 05705。使用广泛的光谱分析和电子圆二色性 (ECD) 计算来阐明 penilline D ( 1 ) 的结构，包括其绝对构型。所有分离的化合物 ( 1 – 12) 评估了它们对乙酰胆碱酯酶 (AChE) 和胰脂肪酶 (PL) 的细胞毒性、抗菌和酶抑制活性。其中，化合物5对143B细胞系表现出中等的体外细胞毒活性，IC ₅₀值为12.64 ± 0.78 μM。化合物6对AChE表现出较强的抑制活性，IC ₅₀值为0.36 nM（他克林的IC ₅₀为18.7 nM），而化合物6和11对PL酶的抑制活性较弱。此外，还在6和 AChE 之间进行了计算机分子对接研究。