Design and synthesis of 1,4-dihydropyridine and cinnamic acid esters and their antioxidant properties

Abstract

In this study, cinnamic acid derivatives with pyridine ring were synthesized via Hantzsch reaction in order to expand conjugation system and their antioxidant abilities were tested. According to the evaluation results of their antioxidant properties, compounds 2 and 3 have similar antioxidant activity to prevent DNA from ^•OH^– and Cu²⁺/GSH induced oxidation, demonstrating that 1,4-dihydropyridine and pyridine nucleus exhibit good resistance to oxidation while the substituents have little effect. In the meantime, the AAPH-induced oxidative DNA damage [AAPH=2,2′-azobis(2-methylpropionamidine)dihydrochloride] and trapping ABTS^+• test show that N—H bond and large conjugation systems are the pivotal parts to improve the activities of antioxidant.

Keywords

Cinnamic acid / 1,4-Dihydropyridine / Free radical / Oxidation / Antioxidant / DNA

References

[1] Mena S., Ortega A., Estrela J. M. Mutat. Res., 2009, 674: 36.

[2] Cooke M. S., Evans M. D., Dizdaroglu M., Lunec J. FASEB J., 2003, 17: 1195.

[3] Sugamura K., Keaney J. F. Free Radic. Biol. Med., 2011, 51: 978.

[4] Murthy Y. L. N., Rajack A., Ramji M. T., Praveen C., Lakshmi K. A. Bioorg. Med. Chem. Lett., 2010, 18: 6016.

[5] Xiao C., Luo X. Y., Li D. J., Lu H., Liu Z. Q., Song Z. G., Jin Y. H. Eur. J. Med. Chem., 2012, 53: 159.

[6] Yang Y., Liu Q. W., Shi Y., Song Z. G., Jin Y. H., Liu Z. Q. Eur. J. Med. Chem., 2014, 84: 1.

[7] Briukhanov V. M., Zverev V. I. Exp. Clin. Pharmacol., 1994, 57: 47.

[8] Hilgeroth A., Lilie H. Eur. J. Med. Chem., 2003, 38: 495.

[9] Kumar B. R. P., Masih P., Karthikeyan E., Bansal A., Vijayan P. Med. Chem. Res., 2010, 19: 344.

[10] Kermani S. A., Shafaroodi H., Miri R., Mirkhani H., Vosooghi M. Med. Chem. Res., 2009, 18: 112.

[11] Tusell J. M., Serratosa J. Brain Res., 1993, 622: 99.

[12] Wächter G. A., Davis M. C., Martin A. R., Franzblau S. G. J. Med. Chem., 1998, 41: 2436.

[13] Desai B., Sureja D., Naliapara Y. S. Bioorg. Med. Chem., 2001, 9: 1993.

[14] Kharkar P. S., Desai B., Gaveria H., Rajesh L., Yogesh N., Anamik S., Kulkarni V. M. J. Med. Chem., 2002, 45: 4858.

[15] Cooper K., Fray M. J., Parry M. J., Richardson K., Steele J. J. Med. Chem., 1992, 35: 3115.

[16] Choi S. J., Cho J. H., Im I., Lee S. D., Jang J. Y., Oh Y. M., Jung Y. K., Jeon E. S., Kim Y. C. Eur. J. Med. Chem., 2010, 45: 2578.

[17] Pan P. C., Cheng M. J., Peng C. F., Huang H. Y., Chen J. J., Chen I. S. J. Nat. Prod., 2010, 73: 890.

[18] Park J. B., Schoene N. Cancer Lett., 2003, 202: 161.

[19] Chen J. J., Chung C. Y., Huang T. L., Chen J. F. J. Nat. Prod., 2009, 72: 107.

[20] Correa W. H., Scott J. L. Green Chem., 2001, 3: 296.

[21] Nakamichi N., Kawashita Y., Hayashi M. Org. Lett., 2002, 4: 3955.

[22] Zhang P., Omaye S. T. Food Chem. Toxicol., 2001, 39: 239.

[23] Li Y. F., Liu Z. Q., Luo X. Y. J. Agric. Food Chem., 2010, 58: 4126.

[24] Li G. X., Liu Z. Q. J. Agric. Food Chem., 2009, 57: 3943.

[25] Halliwell B. Trends Pharmacol. Sci., 2011, 32: 125.

[26] Munoz J. L., Garcia M. F., Varon R., Tudela J., Cánovas G. F., Lopez R. J. N. J. Agric. Food Chem., 2010, 58: 2062.

[27] Yim S. K., Yun S. J., Yun C. H. J. Biochem. Mol. Biol., 2004, 37: 629.

[28] Wang R., Liu Z. Q. J. Org. Chem., 2012, 77: 3952.

[29] Liu Z. H., Wang Y. N., Sun J. B., Yang Y., Liu Q. W., Liu Z. Q., Song Z. G. Chem. Res. Chinese Universities, 2015, 31(4): 526.

[30] Jain A., Alvi N. K., Parish J. H., Hadi S. M. Mutat. Res., 1996, 357: 83.

[31] Zhu B. Z., Kitrossky N., Chevion M. Biochem. Biophys. Res. Commun., 2000, 270: 942.

[32] Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Evans R. C. Free Radical Biol. Med., 1999, 26: 1231.

[33] Shen N., Yan F., Shao W. L., Yang W., Luo G., Yan G. Chem. Res. Chinese Universities, 2014, 30(6): 947.