HSP70 induction by bleomycin metal core analogs |
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| Institution: | 1. 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;2. Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;3. College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan;4. Department of Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto, Kumamoto 862-0976, Japan;1. Hiroshima International University, Faculty of Clinical Nutrition, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan;2. Computer-aided Molecular Modeling Research Center, Kansai (CAMM-Kansai), 3-32-302, Tsuto-Otsuka, Nishinomiya 663-8241, Japan;3. Hiroshima International University, Faculty of Pharmaceutical Sciences, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan;4. Kobe Research Projects on Thrombosis and Haemostasis, 3-15-18, Asahigaoka, Tarumi-ku, Kobe 655-0033, Japan;5. Kobe Gakuin University, Faculty of Pharmaceutical Sciences, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan;1. Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China;2. Department of Mathematics and Statistics, Hang Seng Management College, Hong Kong, China;3. Hong Kong Eye Hospital, Hong Kong, China;1. Genomics Research Center, Academia Sinica, Taipei, Taiwan;2. Department of Chemistry, Faculty of Arts and Sciences, Sakarya University, TR-54187 Sakarya, Turkey;1. Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt |
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| Abstract: | 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. |
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| Keywords: | HSP70 induction Metal chelator Bleomycin PC-12 cells |
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