2023 Fiscal Year Final Research Report

Study on Application of Porphyrin-related molecules to Medicinal Sciences

Research Project

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Project/Area Number	20H03369
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research Institution	Nagoya City University
Principal Investigator	Higuchi Tsunehiko 名古屋市立大学, 大学院薬学研究科, 名誉教授 (50173159)
Co-Investigator(Kenkyū-buntansha)	梅澤直樹名古屋市立大学, 医薬学総合研究院(薬学), 教授 (40347422) 久松洋介名古屋市立大学, 医薬学総合研究院(薬学), 講師 (80587270) 池田慎一名古屋市立大学, 医薬学総合研究院(薬学), 准教授 (90254309)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	bacteriochlorin / near-infrared light / photodynamic therapy / phototoxicity / heme thiolate / prostaglandin / 12-HHT / in-cell catalyst
Outline of Final Research Achievements	We have developed a dye that can be applied to deep cancers that are not covered by conventional photodynamic therapy. Bacteriochlorin (BC), which is similar to porphyrin, has the ability to activate oxygen by irradiation with near-infrared light that can reach deep into the body. As a result of synthesizing three different types of BCs and evaluating their phototoxicity to human cancer cells, it was found that only BC-3 has extremely high phototoxicity. Next, an SR complex with the same coordination structure as cytochrome P450 catalyzed high-speed conversion of PGH2, a common intermediate in prostaglandin (PG) biosynthesis, to 12-HHT, which has a skin wound healing promoting effect. When SR and its analogues were administered to human cells, administration of SR complexes increased the amount of 12-HHT in the cells, suggesting in-cell catalyst and a medicinal function.
Free Research Field	医薬化学　生物無機化学
Academic Significance and Societal Importance of the Research Achievements	生体透過性の高い近赤外光を利用可能なBCで光毒性の極めて高いものが得られたことは、これまでの光線力学療法(PDT)では適用外であった深部がんやサイズの大きいがんへの適用に道を拓く成果となる。PDTは患者への負担の少ない治療法であるため、その社会的意義は大きいと言える。また合成した3種のBCのうち1種のみ光毒性が高かったことは、BCの光毒性の本質解明の手がかりとなり得、学術的意義がある。 SR錯体の細胞への投与により、12-HHTが増産されたことは、実際に細胞内でPGH2から12-HHTへの変換をSR錯体が行ったことを示唆する結果であり、細胞内での錯体の触媒機能が医薬へつながる学術的意義がある。