根據WHO 2020年報告，癌症仍是人類的首要死因，2018年癌症佔全球死因的六分之一。同年確診約1810萬例並預計2040年將增加到2940萬。即便現今發明了不同種類的抗癌藥物，癌症的死亡率仍然居高不下。癌症治療失敗的原因主要來自癌症的多重抗藥性。新藥開發的思路轉移至天然產物。在文獻回顧中，夏枯草在臨床試驗中展現了癌症治療潛力。本研究的目的是從中藥草中尋找一種潛在的逆轉癌症抗藥性的化合物，並著手合成相關衍生物。本研究使用兩種不同的萃取方法進行生物測定引導的粗分層，找出活性分層中的活性物質並設計其衍生物。結果，在活性分層中發現了六種主要化合物，並通過 KBvin cell 中的 SRB 測定發現香豆素是逆轉抗藥性的最有潛力的化合物。比較了19種衍生物的活性，其構效關係可為今後的化學逆轉研究提供基礎。最後，比較 Esculetin 衍生物的 SAR 中，雙取代結構中的兩個衍生物： 6,7-Bis(((E)-3,7-dimethylocta-2,6-dien-1-yl)oxy)-2H-chromen-2-one (97) ( 在10 μM, 20 μM, 與50 μM 時，RF值分別為2.97, 4.85與155.43 )與6,7-Bis(benzyloxy) -2H-chromen-2-one (98) ( 在10 μM, 20 μM, 與50 μM 時，RF值分別為3.36, 4.95與235.47 )可有效逆轉 KBvin 細胞中的紫杉醇抗藥性活性。( Paclitaxel only IC50 = 1862.44 ± 134.76 nM, RF = 1.00 )

Multidrug resistance in cancer will cause treatment ineffectiveness. Prunella vulgaris has shown high potential of anticancer in clinical trials. Aim of the research is to identify a potential lead molecule from Prunella vulgaris for multidrug resistance, and then to design its derivatives. F22 showed the best reversal activity in methanol extract by SRB assay in KBvin. We found five major compounds in our active fraction and discovered coumarins are the most potent compounds. Esculetin has many beneficial effects, such as anticancer. However, there is no literature mentioning that it has the potential to reverse drug resistance in cancer. We designed 19 derivatives and discussed their SAR. The derivatives have no cytotoxicity against HeLa S3 and KBvin cell in SRB assay. Therefore, it can be inferred that the reversal activity is not due to cytotoxicity of the derivatives. Finally, 6,7-Bis(((E)-3,7-dimethylocta-2,6-dien-1-yl)oxy)-2H-chromen-2-one ( 97 ) and 6,7-Bis(benzyloxy)-2H-chromen-2-one ( 98 ) can effectively reverse paclitaxel-resistant activity in KBvin cells. Further exploration of the possible reversal mechanism of drug resistance is necessary.

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