Zhao Wanzhu, Wang Guangfei, Guo Lin, Wang Jingmin, Jing Congcong, Liu Ben, Zhao Feng, Zhang Shumin, Xie Zeping
School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
College of Life Sciences, Yantai University, Yantai 264003, China.
Org Biomol Chem. 2023 Feb 22;21(8):1737-1743. doi: 10.1039/d2ob02247h.
Three novel actinomycins, actimomycin S (1), neo-actinomycins C and D (2 and 3), and one new benzo[]oxazole alkaloid (4) were isolated from the sp. strain S22, along with three known congeners F (5), X (6) and X (7) and 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (8). The structures of the new products were elucidated by spectroscopic methods, and the absolute configuration of amino acid residues was determined by Marfey's analysis. Actinomycin S contains an aspartic acid (Asp) residue in the β-peptidolactone ring. This is the first report of an Asp residue within an actinomycin-type natural product. Notably, neo-actinomycins C and D feature a rare tetracyclic 5-oxazolo[4,5-]phenoxazine chromophore. Among these, neo-actinomycin D, with an unprecedented molecular formula, represents the highest molecular weight member in the actinomycin family. Actinomycins 1-3 exhibited antimicrobial activity against multiple resistant "ESKAPE" pathogens with MIC values ranging from 1.25 to 80.0 μg mL. In addition, 1-3 showed potent cytotoxic activities against the HepG2 liver carcinoma cell line with IC values of 0.10, 0.32, and 0.024 μM, respectively. Furthermore, 1 inhibited cell proliferation by inducing G0-G1 phase arrest in the cell cycle.
从链霉菌属菌株S22中分离出三种新型放线菌素，即放线菌素S（1）、新放线菌素C和D（2和3），以及一种新的苯并[ ]恶唑生物碱（4），同时还分离出三种已知的同系物F（5）、X（6）和X（7）以及2-乙酰氨基-3-羟基-4-甲基苯甲酸甲酯（8）。通过光谱方法阐明了新产物的结构，并通过马尔菲分析法确定了氨基酸残基的绝对构型。放线菌素S在β-肽内酯环中含有一个天冬氨酸（Asp）残基。这是放线菌素类天然产物中首次报道含有Asp残基。值得注意的是，新放线菌素C和D具有罕见的四环5-恶唑并[4,5-]吩恶嗪发色团。其中，新放线菌素D具有前所未有的分子式，是放线菌素家族中分子量最高的成员。放线菌素1-3对多种耐药“ESKAPE”病原体表现出抗菌活性，MIC值范围为1.25至80.0 μg/mL。此外，1-3对肝癌细胞系HepG2显示出强大的细胞毒活性，IC值分别为0.10、0.32和0.024 μM。此外，1通过诱导细胞周期中G0-G1期阻滞来抑制细胞增殖。
