Mu Yu, Jiang Yi, Qu Xiaodan, Liu Bo, Tan Junfeng, Li Guiding, Jiang Mingguo, Li Liya, Han Li, Huang Xueshi
Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University Shenyang 110819 China
Yunnan Institute of Microbiology, Yunnan University Kunming 650091 China
RSC Adv. 2021 Oct 28;11(55):35011-35019. doi: 10.1039/d1ra06182h. eCollection 2021 Oct 25.
Six oxazolomycins (1-6) were isolated from the fermentation broth of a soil-borne bacterial strain, . The structures of the new compounds, oxazolomycins D-F (1-3) and glaucumycins A, B (6a/6b), were elucidated by detailed spectroscopic data analysis. Oxazolomycins 1, 2, 4, and 5 demonstrated weak or modest cytotoxic activities against four human cancer cell lines, with IC values ranging from 10.6 ± 1.7 to 89.5 ± 6.6 μM (or >100 μM). Further study showed that 4 caused S phase cell cycle arrest in SMMC7721 cells through down-regulating the protein expression of cyclin A2, CDK2. Meanwhile, 4 induced apoptosis in SMMC7721 cells through down-regulating the protein levels of Bcl-2, up-regulating the levels of Bax, and activating the cleavage of caspase-3.
从一株土壤细菌菌株的发酵液中分离出了六种恶唑霉素(1-6)。通过详细的光谱数据分析阐明了新化合物恶唑霉素D-F(1-3)和青霉菌素A、B(6a/6b)的结构。恶唑霉素1、2、4和5对四种人类癌细胞系表现出微弱或中等的细胞毒性活性,IC值范围为10.6±1.7至89.5±6.6μM(或>100μM)。进一步研究表明,4通过下调细胞周期蛋白A2、细胞周期蛋白依赖性激酶2的蛋白表达,导致SMMC7721细胞的S期细胞周期阻滞。同时,4通过下调Bcl-2的蛋白水平、上调Bax的水平并激活半胱天冬酶-3的裂解,诱导SMMC7721细胞凋亡。