我們以人類麩胺基硫轉移酶之受質(即榖甘胱肽)類似物為主要骨架，取甘氨酸、絲氨酸和麩氨酸為起始物依序進行耦合反應，進而加以修飾與改變，並且利用Cu(I)-catalyzed設計合成出一系列擁有1,2,3-triazole特質的化合物，最後利用HPLC的純化，可成功得到化合物13-17，總產率約12.8%∼16.5%。
在生物活性測試實驗中，這一系列的化合物對於hGST 的同功酶皆有相當良好的抑制效果；對於hGSTA2其IC50大約在14.3 μM∼164.0 μM左右，而針對hGSTM1則具有更佳的效果，其IC50大約只在1.5 μM∼34.0 μM左右。除此之外，化合物13-17在抑制酵素活性亦有相當不錯的選擇性；如抑制hGSTM1相對於hGSTA2約有3∼20倍的選擇性。其中又以化合物14的抑制效果最為顯著，於hGSTA2其IC50為15.1 μM，hGSTM1則有1.5 μM的效果。且在抑制機制探討的實驗中得知，化合物14抑制hGSTA2，其Ki值為6.4 μM，是屬於競爭型抑制劑，而對hGSTM1其Ki值則為0.6 μM，是為混合式型態抑制劑(即介於競爭型與非競爭型之間)。
另外我們針對人類乳癌細胞 (MDA-MB-231)，進行癌細胞與臨床癌症藥物 (如：順鉑、沙奧特帕等)其抗藥性等相關實驗，證實在我們設計化合物14的存在下，可以幫助減少癌症藥物2∼3倍的用藥劑量，且達到相同之療效。確實使藥物發揮其最大功效，並可大大降低癌症藥物所帶來的副作用。

We choose the substrate, glutathione (γ-Glu-Cys-Gly, GSH), of human glutathione S-transferase (GST) as a building block to synthesize a series of GST substrate-based analogs where the Cys residue is substituted by serine. The overall synthesis was performed by utilizing both Cu(I)-catalyzed Huisgen 1,3-cycloaddition and peptide synthesis technique. Therefore, the final substrate-based analogs 13-17 were comprised of γ-Glu-Ser-Gly backbone, 1,2,3-trizole subunit, and hydrophobic moiety and subject to HPLC purification (total yields 12.8 ~ 16.5%) before biological testing.
In protein level, promising results were displayed in the inhibition of human GST isozyme assay using substrate-based analogs 13-17. In the study of hGSTA2, the IC50 values of 13-17 are found between 14.3 μM and 164.0 μM. In the case of hGSTM1, the IC50 range is observed between 1.5 μM and 34.0 μM indicating the 3- to 20-fold enhancement of inhibitory property of 13-17 toward specific isozyme. Analogue 14, compound with a meta-chlorobenzene moiety as a hydrophobic unit, was the most active one with IC50 values of 15.1 and 1.5 μM toward hGSTA2 and hGSTM1, respectively. From the Lineweaver-Burk plots showed that compound 14 exhibited a competitive inhibition (Ki = 6.4 μM) toward hGSTA2 and also displayed a pattern of mixed-type inhibition (Ki = 0.6 μM) toward hGSTM1 under the same condition.
In cellular study, the cytotoxic effect of antineoplastic agents, cisplatin and thiotepa, in the presence and absence of compound 14 was tested on human breast cancer cell, MDA-MB-231. Evidence of cytotoxicity enhancement (2- to 3-fold) of antineoplastic agents was observed in the presence of 14 suggesting that the hGSTs inhibitor plays an important role in regulating the efficacy of clinical anticancer drugs and reducing the side effect during the cancer therapy.

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