硼中子捕獲治療中應用：利用烯氧基及十二硼烷硫基二鈉(BSH)進行麥可加成反應偶連至葉酸/生物素之可行性研究

Application of Boron Neutron Capture Therapy: A Study on the Michael Addition Reaction Coupling of Allyl Ester and Sodium mercaptoundecahydro-closo-dodecaborate (BSH) to Folic Acid/Biotin

張育賢(Yu-Hsien Chang)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2023年)

https://doi.org/10.6846/tku202300200

摘要

本研究主要在開發潛在應用性之藥物在硼中子捕獲治療(Boron Neutron Capture Therapy; BNCT)，目前此治療方式非醫療界主流處置方案，還是停留在研究階段及零星的恩慈治療，主要改善的方面是精進中子源品質還有含硼藥物在目標細胞的累積與降低毒性。

硼的同位素10B、11B在自然界的含量分別占比約20%:80%；若使用經同位素分離之10B作為原料，成本是十分昂貴的，因此本研究使用未經分離之原料作為起始物用於合成硼酸鈉(Na2B12H11SH)，當目標細胞攝入非同位素分離之藥物還是有2.4個有效的10B可用於治療，在成本考量與量產方面是在未來提供一個方向。

目前臨床研究使用之藥物主要是:BPA(4-Borono-Phenylalanine)、BSH(sodium borocaptate)，我們針對BSH之硫醇官能基作為藥物修飾的目標；透過麥可加成反應將含有烯氧基(Allyl)的葉酸/生物素作為生物標靶結合，期盼能夠在細胞累積更多硼元素並且減少藥物毒性。

關鍵字

硼中子捕獲治療 ； 葉酸 ； 生物素 ； 點擊化學

並列摘要

This study focuses on the development of potential applications of drugs in Boron Neutron Capture Therapy (BNCT). Currently, this treatment method is not widely adopted in the medical field and remains in the research phase and sporadic compassionate therapy. The main improvements aim to enhance the quality of neutron sources and the accumulation of boron drugs in target cells while reducing toxicity.

The isotopes of boron, 10B and 11B, naturally occur in approximate proportions of 20% and 80%, respectively. The use of isotopically separated 10B as a raw material is extremely expensive. Therefore, in this study, we utilized unseparated raw materials to synthesize Sodium mercaptoundecahydro-closo-dodecaborate (Na2B12H11SH). When non-isotopically separated drugs are taken up by target cells, there are still 2.4 effective 10B atoms available for treatment. This approach provides a direction for cost considerations and mass production in the future.

Currently, the drugs mainly used in clinical research are BPA (4-Borono-Phenylalanine) and BSH (sodium borocaptate). We target the thiol functional group of BSH for drug modification. By using the Michael addition reaction, we conjugate folic acid/biotin containing an allyl group as a bio-targeting moiety. We hope to achieve increased accumulation of boron elements in cells and reduced drug toxicity.

並列關鍵字

Boron Neutron Capture Therapy ； Folic acid ； Biotin ； Click chemistry

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