HSP70 induction by bleomycin metal core analogs

Taha F S Ali; Naomi Taira; Kana Iwamaru; Ryoko Koga; Masahiro Kamo; Mohamed O Radwan; Hiroshi Tateishi; Hiromasa Kurosaki; Mohamed Abdel-Aziz; Gamal El-Din A A Abuo-Rahma; Eman A M Beshr; Masami Otsuka; Mikako Fujita

doi:10.1016/j.bmcl.2020.127002

HSP70 induction by bleomycin metal core analogs

Bioorg Med Chem Lett. 2020 Apr 1;30(7):127002. doi: 10.1016/j.bmcl.2020.127002. Epub 2020 Jan 31.

Affiliations

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; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
² 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.
³ College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan.
⁴ Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁵ 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 Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto, Kumamoto 862-0976, Japan. Electronic address: motsuka@gpo.kumamoto-u.ac.jp.
⁶ 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. Electronic address: mfujita@kumamoto-u.ac.jp.

PMID: 32044184
DOI: 10.1016/j.bmcl.2020.127002

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.

Keywords: Bleomycin; HSP70 induction; Metal chelator; PC-12 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bleomycin / analogs & derivatives
Bleomycin / pharmacology
Bleomycin / toxicity
Cell Line, Tumor
HSP70 Heat-Shock Proteins / genetics
HSP70 Heat-Shock Proteins / metabolism*
Histidine / analogs & derivatives*
Histidine / pharmacology*
Histidine / toxicity
Macaca
Pyridines / chemical synthesis
Pyridines / pharmacology*
Pyridines / toxicity
RNA, Messenger / metabolism
Rats

Substances

HSP70 Heat-Shock Proteins
Pyridines
RNA, Messenger
Bleomycin
Histidine