Synthesis and cytotoxicity evaluation of [(2,4-dichlorophenoxy)methyl]-5-aryl-1,3,4-oxadiazole/4H -1,2,4-triazole analogues

We report herein the synthesis, characterization, and cytotoxicity evaluations of some newer oxadiazole andtriazole analogues (5a–j). The cytotoxicity of all the title compounds were evaluated as per the National Cancer Instituteprotocol in a one-dose assay (10 µM) on nine different panels of 59 cancer cell lines. 2-{5-[(2,4-Dichlorophenoxy)methyl]-1,3,4-oxadiazol-2-yl}phenol (5e) showed the maximum cytotoxicity among the series of ten compounds. The cytotoxicityof 5e was comparable to that of the standard anticancer drug, 5-fluorouracil, and better than that of imatinib. Thestructure activity relationship was also discussed.

PDF

___

1. Siegel, R. L.; Miller, K. D.; Jemal, A. CA Cancer J. Clin. 2017, 67, 7-30.
2. Siegel, R. L.; Miller, K. D.; Jemal, A. CA Cancer J. Clin. 2018, 68, 7-30.
3. Arruebo, M.; Vilaboa, N.; Saez-Gutierrez, B.; Lambea, J.; Tres, A.; Valladares, M.; Gonzalez-Fernandez, A. Cancers 2011, 3, 3279-3330.
4. Aydemir, N.; Bilaloglu, R. Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo. Mutat. Res. 2003, 537, 43-51.
5. Bostrom, A.; Hogner, A.; Llinas, A.; Wellner, E.; Plowright, A. T. J. Med. Chem. 2012, 55, 1817-1830.
6. Ahsan, M. J.; Samy, G. J.; Habibullah, K.; Nomani, M. S.; Saraswat, P.; Gaur, R.; Singh, A. Bioorg. Med. Chem. Lett. 2011, 21, 7246-7250.
7. Zhang, K.; Wang, P.; Xuan, L.; Fu, X.; Jing, F.; Li, S,; Liu, Y.; Chen, B. Bioorg. Med. Chem. Lett. 2014, 24, 5154-5156.
8. Khan, M. U.; Akhtar, T.; Al-Masoudi, N. A.; Stoeckli-Evans, H.; Hameed, S. Med. Chem. 2012, 8, 1190-1197.
9. Jones, R. M.; Leonard, J. N.; Buzard, D. J.; Lehmann, J. Expert Opin. Ther. Pat. 2009, 19, 1339-1359.
10. Lee, S. H.; Seo, H. J.; Lee, S. H.; Jung, M. E.; Park, J. H.; Park, H. J.; Yoo, J.; Yun, H.; Na, J.; Kang, S. Y.; et al. Med. Chem. 2008, 51, 7216-7233.
11. Rathore, A.; Sudhakar, R.; Ahsan, M. J.; Ali, A.; Subbarao, N.; Jadav, S. S.; Umar, S.; ShaharYar, M. Bioorg. Chem. 2017, 70, 107-117.
12. Sangshetti, J. N.; Chabukswar, A. R.; Shinde, B. Bioorg. Med. Chem. Lett. 2011, 21, 444-448.
13. Patani, G. A.; LaVoie, E. J. Chem. Rev. 1996, 96, 3147-3176.
14. Warmus, J. S.; Flamme, C.; Zhang, L. Y.; Barrrett, S.; Bridges, A.; Kaufman, M.; Tecle, H.; Gowan, R.; SeboltLeopold, J.; Leopold, W.; et al. Bioorg. Med. Chem. Lett. 2008, 18, 6171-6174.
15. McBriar, M. D.; Clader, J. W.; Chu, I.; Del Vecchio, R. A.; Favreau, L.; Greenlee, W. J.; Hyde, L. A.; Nomeir, A. A.; Parker, E. M.; Pissarnitski, D. A.; et al. Bioorg. Med. Chem. Lett. 2008, 18, 215-219.
16. Ouyang, X.; Chen, X.; Piatnitski, E. L.; Kiselyov, A. S.; He, H. Y.; Mao, Y.; Pattaropong, V.; Yu, Y.; Kim, K. H.; Kincaid, J.; et al. Bioorg. Med. Chem. Lett. 2005, 15, 5154-9.
17. Kaur, R.; Dwivedi, A. R.; Kumar, B.; Kumar, V. Anticancer Agents Med. Chem. 2016, 16, 465-489.
18. Ahsan, M. J.; Choupra, A.; Sharma, R. K.; Jadav, S. S.; Hassan, M. Z.; Bakht, M. A.; Padmaja, P.; Al-Tamini, A. B. S.; Geesi, M. H. Anticancer Agents Med. Chem. 2017, 18, 121-138.
19. Ahsan, M. J.; Ansari, M. Y.; Kumar, P.; Soni, M.; Yasmin, S.; Jadav, S. S.; Sahoo, G. C. Beni-Seuf Univ. J. Basic Appl Sci. 2016, 5, 119-125.
20. Yeung, K. S.; Farkas, M. E.; Kadow, J. F.; Meanwell, N. A. Tetrahedron Lett. 2005, 46, 3429-3432.
21. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. J. Natl. Cancer Inst. 1990, 83, 1107-11012.
22. Boyd, M. R.; Paull, K. D. Drug Dev. Res., 1995, 34, 91-109.
23. Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; et al. J. Nat. Cancer Inst. 1991, 83, 757-766.
24. Shoemaker, R. H. Nat. Rev. Cancer 2006, 6, 813-823.
25. Corona, P.; Carta, A.; Loriga, M.; Vitale, G.; Paglietti, G. Eur. J. Med. Chem. 2009, 44, 1579-1591.