Synthesis and Antitumor Activity of 4-tert-Butyl-5-benzyl-2-benzyliminothiazoles

doi:10.1007/s40242-013-3345-6

Abstract

Abstract:

A series of novel Schiff bases including 4-tert-butyl-5-benzyl-2-benzyliminothiazoles was synthesized by reacting the aromatic aldehydes with the corresponding 2-aminothiazoles. The antitumor bioassay revealed that compounds 2n and 2m exhibited potent cytotoxicity against human cervix cancer(HeLa) cell line with IC₅₀ values of 0.001 and 0.007 mmol/L, respectively. The preliminary structure-activity relationship(SAR) investigations and the apoptosis evaluation suggest that 4-tert-butyl-5-benzyl-2-benzyliminothiazoles may be a satisfactory backbone for antitumor activity, and compound 2n can serve as an attractive candidate for the development of novel apoptosis in anticancer treatment.

Key words: 2-Aminothiazole, Schiff base, Antitumor activity

YE Jiao, QIU Shenyi, HU Aixi, PENG Junmei, QIN Zhi. Synthesis and Antitumor Activity of 4-tert-Butyl-5-benzyl-2-benzyliminothiazoles[J]. Chemical Research in Chinese Universities, 2014, 30(1): 49-54.

References

[1] Holla B. S., Malini K.V., Rao B. S., Sarojini B. K., Kumari N. S., Eur. J. Med. Chem., 2003, 38, 313

[2] Li M., Sim Y., Ham S. W., Bull. Korean Chem. Soc., 2010, 31, 1463

[3] Souza M.V. N. D., J. Sulfur Chem., 2005, 26, 429

[4] Gorczynski M. J., Leal R. M., Mooberry S. L., Bushweller J. H., Brown M. L., Bioorg. Med. Chem., 2004, 12, 1029

[5] Misra R. N., Xiao H. Y., Williams D. K., Kim K. S., Lu S. F., Keller K. A., Mulheron J. G., Batorsky R., Tokarski J. S., Sack J. S., Kimball S. D., Lee F. Y., Webster K. R., Bioorg. Med. Chem. Lett., 2004, 14, 2973

[6] Shao L., Zhou X., Jin Z., Fang J. X., Heteroat. Chem., 2008, 19, 2

[7] Steinberg M., Clinical Therapeutics, 2007, 29, 2289

[8] Lombardo L. J., Lee F. Y., Chen P., Norris D., Barrish J. C., Behnia K., Castaneda S., Cornelius L. A. M., Das J., Doweyko A. M., Fairchild C., Hunt J. T., Inigo I., Johnston K., Kamath A., Kan D., Klei H., Marathe P., Pang S., Peterson R., Pitt S., Schieven G. L., Schmidt R. J., Tokarski J., Wen M. L., Wityak J., Borzilleri R. M., J. Med. Chem., 2004, 47, 6658

[9] Walsby E., Lazenby M., Pepper C., Burnett A. K., Leukemia, 2011, 25, 411

[10] Özkay Y., İncesu Z., Işıkdağ İ., Yeşilkaya M., Cell Biochem. Funct., 2008, 26, 102

[11] Wang P. H., Keck J. G., Lien E. J., Lai M. M. C., J. Med. Chem., 1990, 33, 608

[12] Tang A., Lien E. J., Lai M. M. C., J. Med. Chem., 1985, 28, 1103

[13] Zhou X., Shao L., Jin Z., Liu J. B., Dai H., Fang J. X., Heteroat. Chem., 2007, 18, 55

[14] Hu A. X., Qin Z., Chen P., Ye J., Chin. J. Org. Chem., 2010, 30, 923

[15] Yang L. T., Qin Z., Chen P., Hu A. X., Chin. J. Appl. Chem., 2010, 27, 664

[16] Hu A. X., Xu J. P., Lin H. B., Ye J., The Synthesis and Application of Thiazole Schiff Bases with Nitro-group, CN 101492426, 2009

[17] Hu A. X., Cao G., Ma Y. Q., Zhang J. Y., Ou X. M., Chin. J. Struct. Chem., 2008, 27, 1235

[18] Wang Y., Hu A. X., Cao G., Li G. X., Zhang J. Y., Xia L., Ou X. M., Xu J. B., Chin. J. Org. Chem., 2008, 28, 443

[19] Hu A. X., Cao G., Tetrahedron: Asymmetry, 2011, 22, 1332

[20] Hu A. X., Cao G., Xu J. J., Xia L., He D. H., J. Hunan University, Natural Sciences, 2007, 34, 78