Chinese Journal of Organic Chemistry >
Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues
Received date: 2014-07-29
Revised date: 2014-08-27
Online published: 2014-08-29
Supported by
Project supported by the National Natural Science Foundation of China (No. 81172982).
A series of pyrazol-brigded simplified vinblastine analogues 2a～2m have been synthesized by the reaction of hydrazine derivatives with diformyl intermediates, which were prepared from 2,3,3-trimethyl-3H-indoles using P2O3Cl4/DMF as Vilsmeier-Haack reagent. All the target compounds have been identified by 1H NMR, 13C NMR and HRMS. The preliminary results of anticancer tests indicated that most of the compounds exhibit certain extent of anticancer activity against both MCF-7 (estrogen-positive) and HepG2 cell lines at the concentration of 50 μmol/L, respectively. 2f and 2j are the two best active compounds, where their cell viabilities against MCF-7 cell line are 28.0% and 21.4%, respectively; while against HepG2 cell line, 31.6% and 34.0%, respectively.
Guo Cuiping , Peng Qunlong , Pan Long , Zhang Dongmei , Chen Heru . Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues[J]. Chinese Journal of Organic Chemistry, 2014 , 34(12) : 2505 -2510 . DOI: 10.6023/cjoc201407042
[1] Noble, R. L.; Beer, C. T.; Cutts, J. H. Ann. N. Y. Acad. Sci. 1958, 76, 882.
[2] Svoboda, G. H.; Neuss, N.; Gorman, M. J. J. Am. Pharm. Assoc. 1959, 48, 659.
[3] Dancey, J.; Steward, W. P. Anti-cancer Drugs 1995, 6, 625.
[4] (a) Langlois, N.; Gueritte, F.; Langlois, Y.; Potier, P. J. Am. Chem. Soc. 1976, 98, 7017. (b) Cros, S.; Wright, M.; Morimoto, M.; Lataste, H.; Couzinier, J. P.; Krikorian, A. Semin. Oncol. 1989, 16, 15.
[5] Sasaki, Y.; Kato, D.; Boger, D. L. J. Am. Chem. Soc. 2010, 132, 13533.
[6] Schleicher, K. D.; Sasaki, Y.; Tam, A. Kato, D.; Duncan, K. K.; Boger, D. L. J. Med. Chem. 2013, 56, 483.
[7] Keglevich, P.; Hazai, L.; Kalaus, G.; Szántay, C. Molecules 2012, 17, 5893.
[8] Ngo, Q. A.; Roussi, F.; Thoret, S.; Guéritte, F. Chem. Biol. Drug Des. 2010, 75, 284.
[9] Zheng, J.; Deng, L. J.; Chen, M. F.; Xiao, X. Z.; Xiao, S. W.; Guo, C. P.; Xiao, G. K.; Bai, L. L.; Ye, W. C.; Zhang, D. M.; Chen, H. R. Eur. J. Med. Chem. 2013, 65, 158.
[10] Baradarani, M. M.; Afghan, A.; Zebarjadi, F.; Hasanzadeh, K.; Joule, J. A. J. Heterocycl. Chem. 2006, 43, 1591.
[11] Rashidi, A.; Afghan, A.; Baradarani, M. M.; Joule, J. A. J. Heterocycl. Chem. 2009, 46, 428.
[12] Ye, J. H.; Ye, W. F.; Xiao, C. T.; Chen, Y.; Wang, G. P.; Zhang, W. Chin. J. Org. Chem. 2012, 32, 1503 (in Chinese). (叶家海, 叶文芳, 肖承涛, 陈 雨, 王光普, 张文超, 有机化学, 2012, 32, 1503.)
[13] Kumar, V.; Kaur, K.; Karelia, D. N.; Beniwal, V.; Gupta, G. K.; Sharma, A. K.; Gupta, A. K. Eur. J. Med. Chem. 2014, 81, 267.
[14] Zhang, D. M.; Liu, J. S.; Tang, M. K.; Liu, A.; Cao, H. H.; Jiang, L.; Chan, J. Y.; Tian, H. Y.; Fung, K. P.; Ye, W. C. Eur. J. Pharmacol. 2012, 692, 19.
[15] Gigant, B.; Wang, C. G.; Ravelli, R. B. G.; Roussi, F.; Steinmetz, M. O.; Curmi, P. A.; Sobel, A.; Knossow, M. Nature 2005, 435, 519.
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