Identification of N-arylsulfonylpyrimidones as anticancer agents
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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 GI50 = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean GI50 = 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.
KeywordsN-arylsulfonylpyrimidones N-arylsulfonyltetrahydropyrimidones Anticancer activity Antimitotic agent
This work was supported by Research Fund of the Chungnam National University.
- Erickson HP, O’Brien ET (1992) Microtubule dynamic instability and GTP hydrolysis. Annu Rev Biophys Biomol Struct 21:145–166. https://doi.org/10.1146/annurev.bb.21.060192.001045 CrossRefPubMedGoogle Scholar
- Geneste H, Backfisch G, Braje W, Delzer J, Haupt A, Hutchins CW, King LL, Lubisch W, Steiner G, Teschendorf H-J, Unger L, Wernet W (2006) Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: quinolin(di)one and benzazepin(di)one derivatives. Bioorg Med Chem Lett 16:658–662. https://doi.org/10.1016/j.bmcl.2005.10.035 CrossRefPubMedGoogle Scholar
- Kim I-W, Lee C-K, Kim HS, Jung S-H (2003) Importance of sulfonylimidazolidinone motif of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicity: synthesis of 2-benzoyl-4-phenyl[1,2,5]thiazolidine-1,1-dioxides and their cytotoxcity. Arch Pharm Res 26:9–14. https://doi.org/10.1007/BF03179923 CrossRefPubMedGoogle Scholar
- Subramanian S, Kim N-S, Thanigaimalai P, Sharma VK, Lee K-C, Kang JS, Kim H-M, Jung S-H (2011) Structure-activity relationship studies of novel arylsulfonylimidazolidinones for their anticancer activity. Eur J Med Chem 46:3258–3264. https://doi.org/10.1016/j.ejmech.2011.04.042 CrossRefPubMedGoogle Scholar
- Subramanian S, Sharma VK, Yun J, Jung S-H (2014) Exploration of isosteric replacement of imidazolidinone motif in 4-phenyl-1-arylsul-fonylimidazolidinone with pyrazole and pyrazolidinone for cytotoxicity. Bull Korean Chem Soc 35:2922–2928. https://doi.org/10.5012/bkcs.2014.35.10.2922 CrossRefGoogle Scholar
- Yoon SJ, Chung YH, Lee MS, Choi DR, Lee HS, Yun HR, Lee DK, Moon EY, Hwang HS, Choi CH, Jung S-H (1999) Arylsulfonylimidazolone derivs. as an antitumor agent. US patent 592910327Google Scholar