Design and synthesis of boron-containing drugs and application to dual resonance MRI and neutron capture therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: Aoki Shin 東京理科大学, 薬学部生命創薬科学科, 教授 (00222472)
• Co-Investigator(Renkei-kenkyūsha): HISAMATSU YOSUKE 東京理科大学, 薬学部, 助教 (80587270)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ホウ素中性子捕捉療法 / 天然物 / グルコサミン / ホウ素クラスター / 銅

Outline of Final Research Achievements

Objective of this work is to deliver boron-containing compounds to tumor sites and to detect (visualize) the accumulation of boron in tumor size (in vivo imaging of boron compounds) for boron neutron capture therapy (BNCT). In this work, we have succeeded in the synthesis of sulfoquinovosylacyl-1,3-propanediol (SQAP) having a hydrophobic boron-containing alkyl group containing boron cluster for BNCT and iodo groups for computed tomography (CT). However, tumor accumulation of those SQAP derivatives were low and their toxicity to mouse was detected. Next, design and synthesis of sugar derivatives to target glucose transporters that are overexpressed on cancer cells were conducted. These D-glucosamine analogs are less toxic and some compounds exhibit fairly good T/B (tumor/blood) ratios. It was found that o-carborane undergoes decomposition in the presence of copper(II) ion in aqueous solution at neutral pH to generate 10 B(OH)3, which was applied to 11B MRI probe of Cu2+.

Free Research Field

生物有機化学