Research Center of Chinese Herbal Resource Science and Engineering, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Key Laboratory of Chinese Medicinal Resource from Lingnan, Guangzhou University of Chinese Medicine, Ministry of Education, Guangzhou 510000, China.
Molecules. 2022 May 23;27(10):3348. doi: 10.3390/molecules27103348.
Anthracycline dutomycin is a tetracyclic quinone glycoside produced by NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative, which was identified in our previous research. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate their antiproliferation activities. The results showed that both dutomycin and SW91 block cells at the S phase, whereas dutomycin shows more significant inhibition of cell growth. Their interactions with calf thymus DNA (CT-DNA) were investigated, with dutomycin exhibiting higher binding affinity. The molecular docking demonstrated that the 12-methyl group makes dutomycin attach to the groove of DNA. These findings suggest that dutomycin has binding higher affinity to DNA and impairs DNA replication resulting in more significant antitumor activity.
多柔比星是由 NRRL B-5482 产生的四环醌糖苷。SW91 是 C-12 去甲基多柔比星衍生物，这是我们之前的研究中发现的。我们对这两种化合物进行了体外细胞毒性和细胞凋亡检测，以证明它们的抗增殖活性。结果表明，多柔比星和 SW91 都能使细胞在 S 期停滞，而多柔比星对细胞生长的抑制作用更显著。研究了它们与小牛胸腺 DNA（CT-DNA）的相互作用，结果表明多柔比星具有更高的结合亲和力。分子对接表明，12-甲基使多柔比星与 DNA 沟结合。这些发现表明，多柔比星与 DNA 具有更高的结合亲和力，并且会破坏 DNA 复制，从而产生更显著的抗肿瘤活性。
