Design, synthesis and activities of aziridine derivatives of N⁵-methyltetrahydrofolate against methionine synthase

Abstract

Aziridine derivatives of N⁵-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 and 6 exhibited superior inhibitory activities(IC₅₀: 5.05 and 4.15 µmol/L, respectively) compared to the corresponding chain analogue 4(IC₅₀=24.42 µmol/L). The results suggest that the aziridine derivatives can get potential activities against nucleophilic methionine synthase.

Keywords

Aziridine / Methionine synthase / Ring closure reaction / N⁵-Methyltetrahydrofolate

References

[1] Grabowski M., Banasiuk R., Wegrzyn A., Kedzierska B., Lica J., Banecka-Majkutewicz Z., Banecki B. Acta Biochim. Pol., 2012, 59: 489.

[2] Martha L. L., Rowena G. M. Annu. Rev. Biochem., 1997, 66: 269.

[3] Partearroyo T., Perez-Miguelsanz J., Ubeda N., Valencia-Benitez M., Alonso-Aperte E., Varela-Moreiras G. Eur. J. Nutr., 2013, 52: 1157.

[4] Zhou D., Mei Q., Luo H., Tang B., Yu P. Int. J. Bio. Sci., 2012, 8: 819.

[5] Zhong S., Xu J., Li W., Chen Z., Ma T., Zhao J. Gene, 2013, 531: 8.

[6] Zhang Z. Z., Tang C., Zhou S. X., Wang W., Guo Y., Xia J., Liu Z., Wang B., Wang X. W., Golding B. T., Griff R. J., Du Y. S., Liu J. Y. Eur. J. Med. Chem., 2012, 58: 228.

[7] Banks E. C., Doughty S. W., Toms S. M., Wheelhouse R. T., Nicolaou A. FEBS J., 2007, 274: 287.

[8] Banerjee R. V., Matthews R. G. FASEB J., 1990, 4: 1450.

[9] Deng X., Zhang Z., Wang X., Liu J. J. Peking Univers.(Health Science), 2010, 42(5): 596.

[10] Deng X., Liu W., Li C., Zhang Z., Wang X., Liu J. J. Chin. J. Org. Chem., 2011, 31(1): 75.

[11] Li X. Y., Chen N., Xu J. X. Synthesis, 2010, 20: 3423.

[12] David M. H., Steven P. H., Amber L. T., Tom D. H. Org. Lett., 2008, 10: 3453.

[13] Maité S. V., Pierre L. B., Pierre J., Annie F., Clotilde F. Tetrahedron Asymmetry, 2009, 20: 2077.

[14] Cheng C. C., Lu Y. L. Chem. Commun., 1998, 14: 253.

[15] Zhang Z. L., Wu J., Ran F. X., Guo Y., Tian R., Zhou S. X., Wang X. W., Liu Z. M., Zhang L. R., Cui J. R., Liu J. Y. Eur. J. Med. Chem., 2009, 44: 764.

[16] Persa C., Pierce A., Ma Z., Kabil O., Lou M. F. Exp. Eye Res., 2004, 79: 875.

[17] Drummond J. T., Jarrett J., González J. C., Huang S., Mattews R. G. Anal. Biochem., 1995, 228: 323.

[18] Jarrett J. T., Goulding C. W., Fluhr K., Huang S., Matthews R. G. Method. Enzymol., 1997, 281: 196.