博来霉素金属核心类似物诱导 HSP70。
HSP70 induction by bleomycin metal core analogs.
机构信息
Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan.
出版信息
Bioorg Med Chem Lett. 2020 Apr 1;30(7):127002. doi: 10.1016/j.bmcl.2020.127002. Epub 2020 Jan 31.
Induction of heat shock protein 70 (HSP70) is known to be effective against various diseases. We are interested in HSP70 induction capability of an antitumor antibiotic bleomycin which produces oxidative stress by iron chelate formation and oxygen activation in a cell. The HSP70 induction activity of bleomycin and its six metal core analogs was examined, and a compound HPH-1Trt of 10 μM was found to induce this protein in a pheochromocytoma cell line and some T cell and monocytic cell lines. Its mechanism is increase of HSP70 mRNA, but higher concentration of this compound showed toxicity. Two new derivatives were then synthesized, and one of them named DHPH-1Trt was shown to have less toxicity and higher HSP70 induction activity. This study would lead to a clue for new HSP70 inducer clinically used in near future.
热休克蛋白 70（HSP70）的诱导已被证实对多种疾病有效。我们对通过铁螯合形成和细胞内氧激活产生氧化应激的抗肿瘤抗生素博来霉素的 HSP70 诱导能力感兴趣。我们检测了博来霉素及其六种金属核心类似物的 HSP70 诱导活性，发现浓度为 10μM 的化合物 HPH-1Trt 可诱导嗜铬细胞瘤细胞系以及一些 T 细胞和单核细胞系中这种蛋白的表达。其机制是 HSP70mRNA 的增加，但该化合物的更高浓度显示出毒性。然后合成了两种新的衍生物，其中一种名为 DHPH-1Trt 的衍生物显示出较低的毒性和更高的 HSP70 诱导活性。本研究将为未来临床应用 HSP70 诱导剂提供线索。
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