College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 34134, Republic of Korea.
Department of Pharmaceutical Engineering, Cheongju University, Cheongwon-gu, Cheongju, 28503, Republic of Korea.
Arch Pharm Res. 2018 Mar;41(3):251-258. doi: 10.1007/s12272-018-1003-9. Epub 2018 Jan 13.
For confirming the role of five membered ring of imidazolidinone moiety of N-arylsulfonylimidazolidinones (7) previously reported with highly potent anticancer agent, a series of N-arylsulfonylpyrimidones (10a-g) and N-arylsulfonyltetrahydropyrimidones (11a-e) were prepared and their anti-proliferating activity was measured against human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3) using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4-phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean GI = 0.26 µM) showed best growth inhibitory activity against human cancer cell lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11) exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and comparable activity to N-arylsulfonylimidazolidinones (7). Especially, tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety at position 1 demonstrated their strong growth inhibitory activity against human cancer cell lines.
为了确认先前报道的具有高抗癌活性的 N-芳基磺酰基咪唑烷酮（7）中五元咪唑烷酮部分的作用，合成了一系列 N-芳基磺酰基嘧啶酮（10a-g）和 N-芳基磺酰基四氢嘧啶酮（11a-e），并通过 XTT 测定法测定了它们对人癌细胞系（肾 ACHN、结肠 HCT-15、乳腺 MDA-MB-231、肺 NCI-H23、胃 NUGC-3 和前列腺 PC-3）的增殖抑制活性。其中，1-(1-乙酰基吲哚啉-5-基磺酰基)-4-苯基四氢嘧啶-2(1H)-酮（11d，平均 GI = 3.50µM）和乙基 5-(2-氧代-4-苯基四氢嘧啶-1(2H)-基磺酰基）-吲哚啉-1-羧酸酯（11e，平均 GI = 0.26µM）对人癌细胞系的生长抑制活性最佳。考虑到活性结果，N-芳基磺酰基四氢嘧啶酮（11）比 N-芳基磺酰基嘧啶酮（10）表现出更强的活性，与 N-芳基磺酰基咪唑烷酮（7）相当。特别是在 1 位含有酰基吲哚啉-5-基磺酰基部分的四氢嘧啶-2(1H)-酮类似物对人癌细胞系表现出强烈的生长抑制活性。
