Development of novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kanazawa University
• Principal Investigator: Endo Yoshio 金沢大学, がん進展制御研究所, 准教授 (30211783)
• Co-Investigator(Renkei-kenkyūsha): UTO YOSHIHIRO 徳島大学, 工学部, 准教授 (20304553)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 光線力学的治療 / 5-アミノレブリン酸 / 効果増強

Outline of Final Research Achievements

5-Aminolevulinic acid (ALA) is now widely used for photodynamic diagnosis and photodynamic therapy (ALA-PDT) of various cancers. In the heme biosynthesis pathway, ALA is converted to protoporphyrin IX (PpIX). Following excitation with blue light (405 nm), the accumulated PpIX emits a red fluorescence (635 nm). Thus, cancer tissue can be effectively visualized by the PpIX fluorescence. Furthermore, absorption of light beyond 630 nm by PpIX leads to the production of reactive oxygen species that can induce cell death in various cancer cells. Previously, we found that the Schiff base derivative TX-816 can significantly increase the effect of ALA-PDT by accelerating the intracellular PpIX accumulation. In this study, we synthesized TX-816 derivatives in which 2-chloro-4-nitroaniline was substituted with 4-alkyl aniline. These derivatives were chemically more stable than TX-816 was. The derivatives may become a potent lead compounds for the development of prodrug-type ALA-PDT sensitizers.

Free Research Field

分子腫瘍学