含硼之胜肽衍生物合成與其生物活性之評估(I); 含硼之異腈衍生物之合成(II)

Synthesis and Biological Evaluation of Boron-Containing Peptide-Based Analogues(I); Synthesis of Boron-Containing Isocyanide Analogues(II)

蔡佳驊(Chia-Hua Tsai)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2012年)

https://doi.org/10.6846/TKU.2012.01317

摘要

含硼之胜肽衍生物合成與其生物活性之評估(I)
本論文設計與合成了一系列含硼胜肽化合物。此類化合物可以以簡單的合成方法製備與純化。並且成功合成出系列A 與系列B 之含硼胜肽化合物。
本研究使用了HepG2(肝癌)和MDA-MB231(乳癌)兩種癌細胞，來評估所合成之化合物的抗癌能力。藉由改變含硼化合物之結構來探討分子結構與生物活性之關係。由實驗結果發現，化合物A-07、A-08、A-09、A-11、A-12 對於HepG2 癌細胞具有抑制的效果。
B-38、B-41、B-42 對MDA-MB231 細胞具有抑制效果，其中B-41、B-42 對HepG2 細胞亦具有抑制效果。含硼胜肽化合物之活性測試中，發現(a)取代基對於抑制效果具有重要的影響；(b)在對照組與三種含硼官能基比較中，又以三氟硼酸的抑制效果最好。

含硼之異腈衍生物之合成(II)
本論文設計與合成了含硼異腈化合物。經由一系列合成步驟後，可得到最終產率為
58%。

關鍵字

硼酸 ； 硼酯 ； 三氟硼酸 ； 蛋白酶 ； 胜肽 ； 抗癌 ； 異腈

並列摘要

Synthesis and Biological Evaluation of Boron-Containing
Peptide-Based Analogues(I)
In this research, we have designed and synthesized two series of boron-containing analogues. These compounds could be easily synthesized and purified via simple synthetic operations. In addition, MTT assay was applied to evaluate their biological potencies against HepG2 (liver cancer), and MDA-MB231 (drug resistant breast cancer).
Compounds A-07, A-08, A-09, A-11 and A-12 potent against HepG2(liver cancer) cell line. B-38, B-41, B-42 are active against MDA-MB231(drug resistant breast cancer) cell line and B-41, B-42 are potent against HepG2 cancer cell line. The structure-activity relationship (SAR)indicated that compounds possess lager side chain were generally more potent against either HepG2 or MDA-MB231 cell lines. In addition, inclusion of a potassium trifluoroborate was essential to the compound’s biological activity. In summery, inclusion of a phenylalanine at position 2, a benzyl-protected serine at position 3 and a potassium trifluoroborate generated the most potent compound (B41) against HepG2 and MDA-MB231 cell lines.

Synthesis of Boron-Containing Isocyanide Analogues(II)
In the second project, we have designed and synthesized boron-containing isocyanide. The overall yield was 58% over 9 steps synthetic operations. More boron-containing isocyanide derivatives were being synthesized and their biological evaluation will be reported in due course.

並列關鍵字

boronic acid ； boronic ester ； trifluoroborate ； protease ； proteasome ； peptide ； anti-cancer ； isocyanide

參考文獻

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