THORAYA ABD EL-REHEEM FARGHALY, MAGDA AHMAD ABDALLAH, HUDA KAMEL MMAHMOUD

Synthesis of novel 1,2,4-triazoles and triazolo-thiadiazines as anticancer agents

A new series of 7-arylazo-5$H$-3-(trifluoromethyl)-6-methyl-1,2,4-triazolo-[3,4-$b$]-1,3,4-thiadiazines was prepared by reaction of 4-amino-3-trifluoromethyl-5-mercapto-1,2,4-triazoles with $N$-aryl-2-oxo-propane hydrazonoyl chloride in dioxane under reflux in the presence of triethylamine. Furthermore, Schiff bases of 4-amino-5-mercapto-1,2,4-triazole derivatives were reacted with a variety of hydrazonoyl chlorides and gave the respective hydrazonothioates. In addition, the novel \textit{bis}-(1,2,4-triazole-3-thione) was reacted with the appropriate hydrazonoyl chloride in dioxane under reflux in the presence of triethylamine to give the corresponding \textit{bis}-(1,2,4-triazolethiohydrazonoate). The structures of the new compounds were established based on elemental and spectral data. The mechanism of the studied reaction was also discussed. Moreover, some of the new products were screened for their anticancer activity and the results obtained are promising and indicate that compounds \textbf{4a }and \textbf{4i} are the most active inhibitors against HEPG-2 and compounds \textbf{4a} and \textbf{13b} are active against HCT cell lines.

Anahtar Kelimeler:

4-Amino-3-trifluoromethyl-5-mercapto-1, 2, 4-triazole, hydrazonoyl halides, anticancer activity, triazolo[3, 4-$b$][1, 3, 4]thiadiazines

Synthesis of novel 1,2,4-triazoles and triazolo-thiadiazines as anticancer agents

Keywords:

4-Amino-3-trifluoromethyl-5-mercapto-1, 2, 4-triazole, hydrazonoyl halides, anticancer activity, triazolo[3, 4-$b$][1, 3, 4]thiadiazines,

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Bekircan, O.; Bektas, H. Molecules 2006, 11, 469–477.
Li, Z.; Gu, Z.; Yin, K.; Zhang, R.; Deng, Q.; Xiang. J. Eur. J. Med. Chem. 2009, 44, 4716–4720.
Shawali, A. S.; Abdallah, M. A.; Mosselhi, M. A. N.; Mohamed, Y. F. Z. Naturforsch. 2002, 57B, 552–556.
Dawood, K. M.; Farag A. M.; Abdelaziz, H. A. Heteroatom. Chem. 2005, 16, 621–627.
Abdallah, M. A.; Riyadh, S. M.; Abbas I. M.; Gomha, S. M. J. Chin. Chem. Soc. 2005, 52, 987–994.
Chen, M.; Wang, X.; Wang, S.; Feng, Y.; Chen, F.; Yang, C. J. Fluorine Chem. 2012, 135, 323–329.
Park, B. K.; Kitteringham, N. R.; O’Neill, P. M. Annu. Rev. Pharmacol. Toxicol. 2001, 41, 443–470.
Abdel Hafez, N. A.; Farghaly, T. A.; Al-Omar, M. A.; Abdalla, M. M. Eur. J. Med. Chem. 2010, 45, 4838–4844.
Farghaly, T. A.; Mahmoud, H. K. Arch. Pharm. Chem. Life Sci. 2013, 346, 392–402.
Farghaly, T. A.; Gomha, S. M.; Abbas, E. M.; Abdalla, M. M. Arch. Pharmazie 2012, 345, 117–122.
Farghaly, T. A.; Abdallah, M. A.; Abdel Aziz, M. R. Molecules 2012, 17, 14625–14636.
Riyadh, S. M.; Farghaly, T. A.; Abdallah, M. A.; Abdalla, M. M.; Abd El-Aziz, M. R. Eur. J. Med. Chem. 2010, , 1042–1050.
Riyadh S. M., Farghaly T. A. Tetrahedron 2012, 68, 9056–9060.
Farghaly, T. A.; Abbas, E. M. H.; Dawood, K. M.; El-Naggar, T. B. A. Molecules 2014, 19, 740–755.
Shawali, A. S., Farghaly, T. A., Arkivoc 2008, i , 18–64.
Wang, B.; Liu, X.; Zhang, X.; Zhang, J.; Song, H.; Li, Z. Chem. Biology Drug Design 2011, 78, 42-49.
Demchenko, A. M.; Yanchenko, V. A.; Gutov, A. V.; Chernega, A. N.; Lozinskii, M. O. Zh. Org. Farm. Khim. , 5, 41–46. Cansız, A.; Koparır, M.; Demirda˘g, A. Molecules 2004, 9, 204–212.
Ye, X.; Chen, Z.; Zhang, A.; Zhang, L. Molecules 2007, 12, 1202–1209.
Shi, L.; Fang, R.; Zhu, Z.; Yang, Y.; Cheng, K.; Zhong, W.; Zhu, H. Eur. J. Med. Chem. 2010, 45, 4358–4364.
Molteni, G.; Ponti, A. Tetrahedron: Asymmetry 2004, 15, 3711–3714.
Sharba, A. H. K.; AL-Fattahi, Y. A.; Askar, F. W. Al-Mustansiriya J. Sci. 2011, 22, 109–122.
Awadallah, A. M.; Ferwanah, A. S.; Elsawi, E. A.; Dalloul, H. M. Asian J. Chem. 2002, 14, 1230–1234.
Ferwanah, A. S.; Awadallah A. M.; Khafaja, N. A. Asian J. Chem. 2001, 13, 1203–1207.
Ferwanah, A. S.; Kandile, N. G.; Awadallah A. M.; Miqdad, O. A. Synthetic Commun. 2002, 32, 2017–2022.
Abdallah, M. A.; Mosselhi, M. A. N.; Riyadh, S. M.; Harhash, A. E.; Shawali, A. S. J. Chem. Res. 1998, 700, –3046.
Shawali, A. S.; Abdallah, M. A.; Abbas, I. M.; Eid, G. M. J. Chinese Chem. Soc. 2004, 51, 351–357.
Cretu, O. D.; Barbuceanu, S. F.; Saramet, G.; Draghici. C. J. Serb. Chem. Soc. 2010, 75, 1463–1471.
Eweiss, N. F.; Osman, A. O. J. Heterocycl. Chem. 1980, 17, 1713–1717.
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. J. National Cancer Inst. 1990, 82, 1107–1112.