新型含哌嗪-磺酰胺的2(5H)-呋喃酮类化合物的合成及其抗癌活性

以糠醛为原料，经氧化、醚化和重结晶制得5-甲氧基-3,4-二溴-2(5H)-呋喃酮（4）; 4与哌嗪经Michael加成消除反应制得5-甲氧基-4-哌嗪基-3-溴-2(5H)-呋喃酮（5）； 5与取代磺酰氯经磺酰化反应合成了7 个新型的含哌嗪-磺酰胺的2(5H)-呋喃酮类化合物(7a~7g)，其结构经¹H NMR， ¹³C NMR， IR和HR-MS表征。初步的生物活性研究(MTT法)表明，7a~7g均能显著抑制人宫颈癌Hela细胞的增殖，其中5-甲氧基-4-(对乙酰氨基苯磺酰基-哌嗪基)-3-溴-2(5H)-呋喃酮（7f）的抑制活性最佳，其IC₅₀为0.03 μM(24 h)。

Synthesis and Anticancer Activities of Novel 2 (5H)-furanone Derivatives Containing Piperazine-Sulfonamide

 (S)-3,4-dibromo-5-methoxy-2(5H)-furanone（4） was synthesized by oxidation, etherification and recrystallization， using furfural as the starting material. (S)-3-bromo-5-methoxy-4-(piperazin-1-yl)-2(5H)-furanone（5） was obtained by Michael addition-elimination reactions of 4 with piperazidine. Seven novel 2(5H)-furanone derivatives(7a~7g) containing piperazine-sulfonamide were synthesized by sulfonylation reaction of 5 with substituted sulfochlorides. The structures were characterized by ¹H NMR, ¹³C NMR, IR and HR-MS. The anti-tumor activities against human cervical cancer Hela cell lines were evaluated by MTT method. The results showed that 7a~7g exhibited good inhibition. The IC₅₀ of (S)-N-【4-｛［4-(4-bromo-2-methoxy-5-oxo-2,5-dihydrofuran-3-yl)piperazin-1-yl］sulfonyl｝phenyl】acetamide（7f） was 0.03 μM(24 h).