Synthesis and evaluation of novel N-(4′-arylpyrimidin-2′-yl) sulfonylurea derivatives as potential antifungal agents

Abstract

Sulfonylureas(SUs) are potent and selective inhibitors of acetohydroxyacid synthase and has been used as herbicides. Some SUs also displayed other biological activities. In order to discuss the antifungal activity of SUs, a series of novel SUs containing aryl-substituted pyrimidine moieties was designed and synthesized. The preliminary bioassay showed that the title compounds exhibited moderate to favorable fungicidal activities in vivo. Especially, compound 9b exhibited more efficacy than the controls against five fungi at 25 mg/L. These promising results indicate that an aryl group on pyrimidine ring is favorable for antifungal activity and SUs are potential inhibitors for some phytopathogenic fungi.

Keywords

Acetohydroxyacid synthase / Sulfonylurea / Fungicidal activity / Substituted pyrimidine

References

[1] McCourt J A, Duggleby R G. Amino Acids, 2006, 31: 173.

[2] Pue N, Guddat L W. Curr. Pharm. Des., 2014, 20: 740.

[3] Liu Z, Pan L, Li Y H, Wang S H, Li Z M. Chem. Res. Chinese Universities, 2013, 29(3): 466.

[4] Chipman D, Barak Z A, Schloss J V. Biochim. Biophys. Acta, 1998, 1385: 401.

[5] Guo X H, Jia K L, Dan W Y, Li J F. Chem. Eng., 2012, 9: 25.

[6] Lafontaine Y, Beauvais C, Cessna A J, Gagnon P, Hudon C, Poissant L. Sci. Total Environ., 2014, 479/480: 1.

[7] Grandoni J A, Marta P T, Schloss J V. J. Antimicrob. Chemother., 1998, 42: 475.

[8] Kingsbury J M, Yang Z H, Ganous T M, Cox G M, McCusker J H. Microbiol., 2004, 150: 1547.

[9] Kingsbury J M, McCusker J H. Microbiol., 2010, 156: 929.

[10] Boigegrain R A, Liautard J P, Kohler S. Antimicrob. Agents Chemother., 2005, 49: 3922.

[11] Bange F C, Brown A M, Jacobs W R Jr. Infect. Immun., 1996, 64: 1794.

[12] Kingsbury J M, Goldstein A L, McCusker J H. Euk. Cell, 2006, 5: 816.

[13] Awasthy D, Gaonkar S, Shandil R K, Yadavr, Bharath S, Marcel N, Subbulakshmi V, Sharma U. Microbiol., 2009, 155: 2978.

[14] Atkins T, Prior R G, Mack K, Russell P, Nelson M, Oyston P C F, Dougan G, Titball R W. Infect. Immun., 2002, 70: 5290.

[15] Duggleby R G, Pang S S, Yu H, Guddat LW. Eur. J. Biochem., 2003, 270: 2895.

[16] Pan L, Jiang Y, Liu Z, Liu X H, Liu Z, Wang G, Li Z M, Wang D. Eur. J. Med. Chem., 2012, 50: 18.

[17] Wang D, Pan L, Cao G, Lei H, Meng X H, He J F, Dong M, Li Z M, Liu Z. Inter. J. Antimicrob. Agents, 2012, 40: 463.

[18] Pang S S, Duggleby R G, Guddat L W. J. Mol. Biol., 2002, 317: 249.

[19] Pang S S, Guddat L W, Duggleby R G. J. Biol. Chem., 2003, 278: 7639.

[20] McCourt J A, Pang S S, Duggleby R G. Biochem., 2005, 44: 2330.

[21] Levitt G, Baker D, Fenyes J, Moberg W. Synthesis and Chemistry of Agrochemicals II, 1991, Washington D. C.: American Chemical Society 16.

[22] Li Z M, Ma Y, Guddat L, Cheng P Q, Wang J G, Pang S S, Dong Y H, Lai C M, Wang LX, Jia G F, Li Y H, Wang S H, Liu J, Zhao W G, Wang B L. Pest. Manag. Sci., 2012, 68: 618.

[23] Ungureanu M, Moldoveanu C C, Poeata A, Drochioiu G, Petrovanu M, Mangalagi I I. Ann. Pharm. Fr., 2006, 64: 287.

[24] Akbas E, Berber I, Akyazi I, Anil B, Yildiz E. Lett. Org. Chem., 2011, 8: 663.

[25] McCourt J A, Pang S S, King-Scott J, Guddat L W, Duggleby R G. Proc. Natl. Acad. Sci., 2006, 103: 569.

[26] Chen Q F, Zhang H D, Gong S C. Chin. J. Appl. Chem., 2011, 8: 382.

[27] Zheng Z Y, Chen J Y, Liu G L, Li Y H, Li Z M. Chin. J. Pest. Sci., 2012, 14: 607.

[28] Mayer H, Hamprecht G, Westphalen K O, Gerber M, Walter H. (Phenylsulfonylureido)triazine or -Pyrimidine Herbicides, 1994.

[29] Pan L, Liu Z, Chen Y W, Li Y H, Li Z M. Chem. J. Chinese Universities, 2013, 34(6): 1416.

[30] Liu Z, Pan L, Yu S J, Li Z M. Chem. J. Chinese Universities, 2013, 34(8): 1868.

[31] Chen N C. Bioassay of Pesticides, 1991, Beijing: Beijing Agricultural University Press 161.

[32] Peng H, Deng X Y, Gao L, Tan X S, He H W. Chem. Res. Chinese Universities, 2014, 30(1): 82.