Synthesis and Anticancer Activity of Isatin, Oxadiazole and 4-Thiazolidinone Based Conjugates

https://doi.org/10.23939/chcht09.01.029
Received: June 30, 2014
Revised: August 28, 2014
Accepted: October 03, 2014
Authors: 
Maryan Lelyukh, Dmytro Havrylyuk and Roman Lesyk

Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University 69, Pekarska str., 79010 Lviv, Ukraine; dr_r_lesyk@org.lviv.net, roman.lesyk@gmail.com

Following the N-alkylation reaction of starting 2-chloro-N-(5-aryl-1,3,4-oxadiazol-2-yl)-acetamides 1a-c with 2,4-thiazolidinedione or 5-sudstituted isatins the corresponding non-condensed oxadiazole derivatives with thiazolidine 2a-c or isatin 4a-h fragments were synthesized. The obtained compounds have been used in Knoevenagel condensation with 5R-isatin (for 2a-c) or 4-thiazolidinone derivatives (for 4a-h) for synthesis of the appropriate 5-ylidenederivatives 3a-g, 5a-k and 6a-d. Anticancer activity of eight synthesized compounds was evaluated toward 60 human tumor cell lines panel in National Cancer Institute.

[1] Pandeya S., Smitha S., Jyoti M. et al.: Acta Pharm., 2005, 55, 27.
[2] Lesyk R. and Zimenkovsky B.: Curr. Org. Chem., 2004, 8, 1547.
[3] Mhaske P., Shelke S., Jadhav R. et al.: J. Heterocyclic Chem., 2010, 47, 1415.
[4] Karali N., Guzel O., Ozsoy N. et al.: Eur. J. Med. Chem., 2010, 45, 1068.
[5] Vintonyak V., Warburg K., Over B. et al.: Tetrahedron, 2011, 67, 6713.
[6] Hassan A., Abdel-Latif F., Nour El-Din A. et al.:  J. Heterocyclic Chem., 2011, 48, 1050.
[7] Vine K., Matesic L., Locke J. et al.: Anti-Cancer Agents Med. Chem., 2009, 9, 397.
[8] Havrylyuk D., Zimenkovsky B., Vasylenko O. et. al.: Eur. J. Med. Chem., 2009, 44, 1396.
[9] Havrylyuk D., Mosula L., Zimenkovsky B. et. al.: Eur. J. Med. Chem., 2010, 45, 5012.
[10] Ramshid P., Jagadeeshan S., Krishnan A. et al.: Med. Chem., 2010, 6, 306.
[11] Havrylyuk D., Kovach N., Zimenkovsky B. et. al.: Arch. Pharm. Chem. Life Sci., 2011, 344, 514.
[12] Wang S., Zhao Y., Zhang G. et.al.: Eur. J. Med. Chem., 2011, 46, 3509.
[13] Lockman J., Reeder M., Robinson R. et. al.: Bioorg. Med. Chem. Lett., 2011, 21, 1724.
[14] Wang S., Zhao Y., Zhu W. et. al.: Arch. Pharm. Chem. Life Sci., 2012, 345, 73.
[15] Kumar D., Sundaree S., Johnson E. et. al.: Bioorg. Med. Chem. Lett., 2009, 19, 4492.
[16] Mosula L., Zimenkovsky B., Havrylyuk D. et. al.:  Farmacia, 2009, 57, 321.
[17] Solomon V., Hu C. and Lee H.: Bioorg. Med. Chem. 2009, 17, 7585.
[18] Kucukguzel S., Kucukguzel I., Tatar E. et. al.: Eur. J. Med. Chem., 2007, 42, 893.
[19] Jha K., Samad A., Kumar Y. et al.: Eur. J. Med. Chem., 2010, 45, 4963.
[20] Navarrete-Vasquez G., Molina-Salinas G., Duarte-Fajardo Z. et. al.:  Bioorg. Med. Chem., 2007, 15, 5502.
[21] Zhang Z., Zhang X.-W., Zhao Z.-Z. et al.: Bioorg. Med. Chem., 2012, 20, 3359.
[22] Dash S., Kumar B., Singh J. et al.: Med. Chem. Res., 2011, 20, 1206.
[23] Gurupadaswamy H., Girish V., Kavitha C. et al.: Eur. J. Med. Chem., 2013; 63, 536.
[24] Bondock S., Adel S., Etman H. et al.: Eur. J. Med. Chem., 2012, 48, 192.
[25] Boyd M. and Paull K.: Drug Dev. Res. 1995, 34, 91.
[26] Shoemaker R.: Nature Reviews / Cancer, 2006, 6, 813.
[27] Lesyk R., Zimenkovsky B., Subtelna I. et al.: Acta Pol. Pharm, Drug Res., 2003, 6, 457.
[28] Karpenko A., Dorovskykh I., Shibinskaya M. et al.: Ukr. Bioorg. Acta, 2008, 2, 65.