Synthesis, crystal structure and biological activities of naproxen-eugenol ester prodrug

Abstract

The prodrug, naproxen-eugenol ester, was synthesized by acyl chloride method with naproxen and eugenol as the raw materials. The structure was identified by proton nuclear magnetic resonance(¹H NMR), mass spectrometry(MS), infrared spectrometry(IR) and X-ray diffraction. The compound was crystallized in the orthorhombic system, space group P2₁2₁2₁ with unit cell dimensions a=0.60563(12) nm, b=1.0234(2) nm, c=3.2654(7) nm, α=90°, β=90°, γ=90°, V=2.0240(7) nm³, Z=4. Calculated density 1.235 Mg/m³; absorption coefficient: 0.083 mm⁻¹; F(000)=800; final R ₁=0.0564. The analgesic activity and anti-inflammatory were similar to those of naproxen, and the results of ulcerogenic activity indicate that the prodrug can significantly decrease the irritation after oral administration.

Keywords

Naproxen-eugenol ester / Crystal structure / Biological activity

References

[1] Pan H. Strait Pharmaceutical Journal, 2005, 17(2): 105.

[2] Zhao J. F. Chinese Journal of Clinical Rational Drug Use, 2011, 4(6): 159.

[3] Shanbhag V. R., Crider A. M., Gokhale R., Harpalani A., Dick R. M. J. Pharm. Sci., 1992, 81(2): 149.

[4] Lau W. M., White A. W., Gallagher S. J., Donaldson M., McNaughton G., Heard C. M. Curr. Pharm. Des., 2008, 14(8): 794.

[5] Huang Z. J., Velazquez C. A., Abdellatif K. R. A., Chowdhur M. A., Reisz J. A., DuMond J. F., King S. B., Knaus E. E. J. Med. Chem., 2011, 54(5): 1356.

[6] Bonina F. P., Puglia C., Barbuzzi T., Caprariis P., Palagiano F., Rimoli M. G., Saija A. Eur. J. Pharm. Sci., 2001, 14(2): 123.

[7] Sheha M., Khedr A., Elsherief H. Eur. J. Pharm. Sci., 2002, 17(3): 121.

[8] Yan T., Yu G. P., Liu P. F., Xiong L. X., Yu S. J., Li Z. M. Chem. Res. Chinese Universities, 2012, 28(1): 53.

[9] Li H. X., Chen X. T., Xu L. Z. Chem. Res. Chinese Universities, 2011, 27(3): 431.

[10] Sun Y., Huang D. W., Li X. H., Hu J. E., Xiu Z. L. Chem. Res. Chinese Universities, 2012, 28(1): 108.

[11] Chen Z., Kwong A. K. Y., Yang Z. J., Zhang L. R., Lee H. C., Zhang L. H. Chem. J. Chinese Universities, 2012, 33(6): 1226.

[12] Li C., Li X., Liu Y. S., Yu F., Han J. L., Hu B., Ye M., Wang Q., Du S. W., Jin N. Y. Chem. J. Chinese Universities, 2011, 32(1): 95.

[13] Cioli V., Putzolu S., Rossi V., Corradino C. Toxicology and Applied Pharmacology, 1980, 54(2): 332.

[14] Xiang L., Wu B., Deng Y. West China Journal of Pharmaceutical Sciences, 2006, 21(2): 178.

[15] Qiu D., Zhang K. H., Fang B. H. Progress in Veterinary Medicine, 2007, 28(8): 101.

[16] Sheldrick G. M., SHELXTL V5.1, Software Reference Manual, Brucker Axs Inc., Madision, 1997