Synthesis of 3S-Substituted Triazino[5,6-b]indoles and 4-Thiazolidinone-triazino[5,6-b]indole Hybrids with Antitumor Activity

Authors: 

Stefan Harkov, Dmytro Havrylyuk and Roman Lesyk

The synthesis and antitumor activity screening of 1,2,4-triazino[5,6-b]indoles based conjugates were performed. Reaction between 3-mercapto-1,2,4-triazino[5,6-b]indoles and several N-arylchloroacetamides yielded 3S-substituted 1,2,4-triazino[5,6-b]indoles. Based on 3-hydrazine-1,2,4-triazino[5,6-b]indoles the new 4-thiazolidinones have been synthesized. Seven synthesized compounds were tested for their anticancer activity in NCI60 cell lines.

[1] Pandeya S., Smitha S., Jyoti M. et al.: Acta Pharm., 2005, 55, 27.
[2] Kinsman O., Livermore D. and Smith C.: Antimicrobial Agents and Chemotherapy, 1993, 37, 1243.
[3] Gladych J., Hornby R., Hunt J. et al.: J. Med. Chem., 1972, 15, 277.
[4] DiCiollo C., Zarembo J. and Pagano J.: Xenobiotica, 1973, 3, 171.
[5] Monge1 A., Palop J., Ramirez C. et al.: Eur. J. Med. Chem., 1991, 26, 179.
[6] Zhang Q., Ding D., Zeng S. et al.: Plos One, 2012, 7(10): e46294.
[7] Zhang Q., Zeng S. Zhang Yu et al.: EMBO Molecular Medicine, 2012, 4, 298.
[8] Lesyk R. and Zimenkovsky B.: Curr. Org. Chem., 2004, 8, 1547.
[9] Havrylyuk D., Zimenkovsky B. and Lesyk R.: Phosphorus, Sulfur Silicon Relat. Elem., 2009, 184, 638.
[10] Kaminskyy D., Khyluk D., Vasylenko O. and Lesyk R.: Tetrahedron Lett., 2012, 53, 557.
[11] Kaminskyy D., Khyluk D., Vasylenko O. et.al.: Sci. Pharm., 2011, 79, 763.
[12] Lesyk R., Zimenkovsky B., Kaminskyy D. et.al.: Biopolymers and Cell, 2011, 27, 107.
[13] Havrylyuk D., Mosula L., Zimenkovsky B. et. al.: Eur. J. Med. Chem., 2010, 45, 5012.
[14] Mosula L., Zimenkovsky B., Havrylyuk D. et. al.: Farmacia, 2009, 57, 321.
[15] Havrylyuk D., Zimenkovsky B., Vasylenko O. et. al.: Eur. J. Med. Chem., 2009, 44, 1396.
[16] Panchuk R., Chumak V., Fil’ M. et. al.: Biopolymers and Cell, 2012, 28, 121.
[17] Havrylyuk D., Zimenkovsky B., Vasylenko O. et. al.: J. Med. Chem., 2012, 55, 8630.
[18] Havrylyuk D., Kovach N., Zimenkovsky B. et. al.: Arch. Pharm. Chem. Life Sci., 2011, 344, 514.
[19] Popov-Pergal K., Cekovic Z. and Pergal M.: Zh. Obsh. Khim., 1991, 61, 1958.
[20] Monks A., Scudiero D., Skehan P. et. al.: J. Nat. Cancer Inst., 1991, 83, 757.
[21] Boyd M. and Paull K:., Drug Dev. Res., 1995, 34, 91.
[22] Shoemaker R.: Nature Rev./Cancer, 2006, 6, 813.
[23] Rostom S.: Bioorg. Med. Chem., 2006; 14, 6475.