| 摘要: | 為延續本實驗室一系列carbazole類衍生物之化學合成及其抗癌活性的探討，著者合成一系列3,6-substituted 9-trimethoxybenzylcarbazole，以及9-trimethoxybenzyl以不同芳基甲基取代的carbazole衍生物，並探討所合成的化合物之抗癌活性。
首先，合成方法以carbazole為起始物，與3,4,5-trimethoxybenzylchloride反應生成9-trimethoxybenzylcarbazole (1)，接著將化合物1以POCl3/DMF進行Vielsmeir formylation得化合物1a，將化合物1a以NaBH4進行還原反應得到化合物1d。將化合物1在AlCl3與醋酸酐存在下進行乙醯化反應，得單乙醯化合物1b及雙乙醯化合物1c。
此外，另將carbazole與arylmethyl chloride反應，得到相對應的化合物9-arylmethyl carbazole (2-5)，將化合物2-5以POCl3/DMF進行Vielsmeir formylation得化合物2a-5a，接著將化合物2a-5a以NaBH4進行還原反應得到相對應的化合物2d-5d。
將這些合成之化合物進行抗癌活性測試，結果顯示部分化合物具明顯的抗癌活性，其中化合物(9-(3,4,5-trimethoxybenzyl)-9H-carbazol-3-yl)methanol (1d)對血癌細胞HL-60及K562、肝癌細胞Hep3B、乳癌細胞MCF7、卵巢癌細胞2774及SKOV3、肺癌細胞H226、H460之抑制活性IC50皆可達10-7-10-9 M，因此化合物1d相當值得進一步探討其抗癌活性。
In order to continue our investigation of novel anticancer agents and their anticancer activities, we synthesized a series of 3,6-substituted 9-trimethoxy benzylcarbazole and 9-arylmethylcarbazole and evaluated for their anticancer activities.
Initially, reaction of carbazole and 3,4,5-trimethoxybenzylchloride yields 9-trimethoxybenzylcarbazole (1). Subsequently, compound 1 underwent Vielsmeir formylation by treating with POCl3/DMF to give compound 1a. Compound 1a underwent reduction by treating with NaBH4 to give compound 1d, and compound 1 was treated with AlCl3 /acetic anhydride yield monoacetyl product 1b and diacetyl product 1c.
Furthermore, reaction of carbazole and arylmethyl chloride yields corresponding 9-arylmethylcarbazoles (2-5). Compounds 2-5 underwent Vielsmeir formylation by treating with POCl3/DMF to give corresponding compounds 2a-5a. Compounds 2a-5a underwent reduction by treating with NaBH4 to give corresponding compounds 2d-5d.
These synthesized compounds were evaluated for their cytotoxicity. Some of these tested compounds were found to demonstrate significant cytotoxicity. The most potent compound (9-(3,4,5-trimethoxybenzyl)-9H-carbazol-3-yl)methanol (1d) demonstrated strong cytotoxic effect with IC50 values in 10-7 to 10-9 M against human leukemia cell HL-60, human hepatoma cell Hep3B, breast cancer cell MCF7, ovarian cancer cell 2774, SKOV3 and lung cancer cell H226, H460. Therefore compound 1d was selected for further investigation. |
