SIOC English
有机化学
高级检索

有机化学 >

2015 , Vol. 35 >Issue 6: 1310 - 1319

DOI: https://doi.org/10.6023/cjoc201412011

研究论文

杂环酮腙与类似物的合成及其对结核杆菌的抑制活性

  • 李忠洲 ,
  • 赵升 ,
  • 李新军 ,
  • 王翠翠 ,
  • 姚璐璐 ,
  • 金瑞良 ,
  • 邹新琢
展开
  • a 华东师范大学化学系 上海 200241;
    b 同济大学附属上海肺科医院上海市结核病(肺)重点实验室 上海 200433

收稿日期: 2014-12-04

  修回日期: 2015-01-21

  网络出版日期: 2015-02-02

收起

Synthesis and Anti-mycobacterial Activities of Heterocyclic Hydrazones and Their Bioisosteric Compounds

  • Li Zhongzhou ,
  • Zhao Sheng ,
  • Li Xinjun ,
  • Wang Cuicui ,
  • Yao Lulu ,
  • Jin Ruiliang ,
  • Zou Xinzhuo
Expand
  • a Department of Chemistry, East China Normal University, Shanghai 200241;
    b Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433

Received date: 2014-12-04

  Revised date: 2015-01-21

  Online published: 2015-02-02

Fold

摘要

22个新的杂环酮腙及其类似物被合成, 其对结核分枝杆菌菌株H37Rv的抑菌活性被测定. 这些化合物都显示出抑菌活性. 其中, 化合物(1E,4E)-1,5-二(5'-溴-2'-噻吩基)-1,4-戊二烯-3-酮-(1',4',5',6'-四氢嘧啶基)腙(1d)的MIC90为2 μg/mL, 显示出最高的抑菌活性; 同时该化合物对单耐异烟肼菌株242、耐多药菌株2312和广泛耐药菌株1220的MIC90值分别为0.25, 1.0和0.5 μg/mL, 也表现出很好的抑菌作用.

关键词： 杂环酮腙; 合成; 结核分枝杆菌; 抑菌活性

本文引用格式

李忠洲 , 赵升 , 李新军 , 王翠翠 , 姚璐璐 , 金瑞良 , 邹新琢 . 杂环酮腙与类似物的合成及其对结核杆菌的抑制活性[J]. 有机化学, 2015 , 35(6) : 1310 -1319 . DOI: 10.6023/cjoc201412011

Abstract

A total of 22 new heterocyclic hydrazones and their bioisosteric compounds were synthesized and evaluated for their activity against Mycobacterium tuberculosis, strain H37Rv. All newly synthesized compounds showed inhibitory activities. Among these compounds, (1E,4E)-1,5-bis(5-bromo-2-thiophenyl)-1,4-pentadiene-3-one-(1,4,5,6-tetrahydro-2-pyrimi- dimyl)-hydrazone (1d) showed the most effective anti-tubercular activity with MIC90 value of 2 μg/mL, and exhibited an excellent inhibitory activity against isoniazid-resistant strain 242, multidrug-resistant strain 2312, and extensively drug-resistant strain 1220 with MIC90 values of 0.25, 1.0 and 0.5 μg/mL, respectively.

Key words： heterocyclic hydrazone analogs; synthesis; Mycobacterium tuberculosis; anti-mycobacterial activity

参考文献

[1] Boogaard, J.; Kibiki, G. S.; Kisanga, E. R.; Boeree, M. J.; Aarnoutse, R. E. Antimicrob. Agents Chemother. 2009, 53, 849.
[2] Palmer, B. D.; Thomposon, A. M.; Sutherland, H. S.; Blaser, A.; Kmentova, I.; Franzblau, S. G.; Wan, B. J.; Wang, Y. H.; Ma, Z. K.,; Denny, W. A. J. Med. Chem. 2010, 53, 282.
[3] Sethi, A.; Yadav, S.; Sharma, R. K. Int. J. Pharm. Sci. Rev. Res. 2010, 6, 117.
[4] Zhang, J.; Angala, S. K.; Pramanik, P. K.; Li. K.; Crick, D. C.; Liav, A.; Jozwiak, A.; Swiezewska, E.; Jackson, M.; Chatterjee, D. ACS Chem. Biol. 2011, 6, 819.
[5] Liu, Y. X.; Xiao, C. L.; Wang, Y. X.; Li, Y. H.; Yang, Y. H.; Li, Y. B.; Bi, C. W.; Gao, L. M.; Jiang, J. D.; Song, D. Q. Eur. J. Med. Chem. 2012, 52, 151.
[6] Oliveira, K. N.; Chiaradia, L. D.; Martins, P. G.; Mascarello, A.; Cordeiro, M. N.; Guido, R. V.; Andricopula, A. D.; Yunes, R. A.; Nunes, R. J.; Vernal, J.; Terenzi, H. Med. Chem. Commun. 2011, 2, 500.
[7] Srivastav, M. K.; Shantakumar, S. M. Chem. Sci. Trans. 2013, 2, 1056.
[8] Torres, E.; Moreno, E.; Ancizu, S.; Barea, C.; Galiano, S.; Aldana, I.; Monge, A.; Perez-Silanes, S. Bioorg. Med. Chem. Lett. 2011, 21, 3699.
[9] Sasaki, H.; Haraguchi, Y.; Itotani, M.; Kuroda, H.; Hashizume, H.; Tomishige, T.; Kawasaki, M.; Masumoto, M.; Komatsu, M.; Tsubouchi, H. J. Med. Chem. 2006, 49, 7854.
[10] WHO Global Tuberculosis Report 2012. Available at: http://www.who.int/tb/publications/global_report/en/.
[11] Servusova, B.; Vobickova, J.; Paterova, P.; Kubicek, V.; kunes, J.; Dolezal, M.; Zitko, J. Bioorg. Med. Chem. Lett. 2013, 23, 3589.
[12] Ahsan, M. J.; Samy, J. G.; Khalilullah, H.; Bakht, M. A.; Hassan, M. Z. Eur. J. Med. Chem. 2011, 46, 5694.
[13] Manvar, A.; Bavishi, A.; Radadiya, A.; Patel, J.; Vora, V.; Dodia, N.; Rawal, K.; Shah, A. Bioorg. Med. Chem. Lett. 2011, 21, 4728.
[14] Simone, P. M.; Starke, J. R.; Vernon, A. A. Am. J. Respir. Crit. Care Med. 2003, 167, 62.
[15] Saquib, M.; Gupta, M. K.; Sagar, R.; Prabhakar, Y. S.; Shaw, A. K.; Kumar, R.; Maulik, P. R.; Gaikwad, A. N.; Sinha, S.; Srivastava, A. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. J. Med. Chem. 2007, 50, 2942.
[16] Huang, X.; Huang, H.; Li, H.; Sun, X.; Huang, H.; Lu, Y.; Long, Y.; She, Z. Org. Lett. 2013, 15, 721.
[17] Koul, A.; Vranckx, L.; Dendouga, N.; Balmans, W.; Wyngaert, I.; Vergauwen, K.; Gohlmann, H.; Willebrords, R.; Poncelet, A.; Guillemont, J.; Bald, D.; Andries, K. J. Biol. Chem. 2008, 283, 25273.
[18] Dixit, P. P.; Patial, V. J.; Nait, P. S.; Jain, S.; Sinha, N.; Arora, S. K. Eur. J. Med. Chem. 2006, 41, 423.
[19] Pieter, C.; Davie, C.; Blaise, M. M.; Jan, J.; Birgit, M.; Vanessa, M.; Luc, V.; Kris, H.; Norbert, D. K. Eur. J. Med. Chem. 2013, 67, 98.
[20] Hwang, J.; Oh, T.; Kaneko, T.; Upton, A.; Franzblau, S.; Ma, Z.; Cho, S.; Kim, P. J. Nat. Prod. 2013, 76, 354.
[21] Ma, Z.; Lienhardt, C.; Mcllleron, H.; Nunn, A. J.; Wang, X. Lancet 2010, 275, 2100.
[22] Chen, S.-J.; Cui, J.-G.; Li, Y.; Fan, L.-H. Chin. J. Org. Chem. 2011, 31, 187 (in Chinese). (陈思静, 崔建国, 李莹, 范良华, 有机化学, 2011, 31, 187.)
[23] Bo, Z.-S.; Wang, D.-X. The Research Development of New Heterocyclic Pesticides and Synthetic Method, Chemical Industry Press, Beijing, 2004, pp. 179～184 (in Chinese) (柏再苏, 王大翔, 新杂环农药的研究发展及合成方法, 化学工业出版社, 北京, 2004, pp. 179～184.)
[24] Zhao, S. M.S. Thesis, East China Normal University, Shanghai, 2008 (in Chinese). (赵升, 硕士论文, 华东师范大学, 上海, 2008.)
[25] Zhang W.-S.; Li, A.-L. Medicinal Chemistry, Higher Education Press, Beijing, 1999, pp. 555～556 (in Chinese). (仉文升, 李安良, 药物化学, 高等教育出版社, 北京, 1999, pp. 555～556.)
[26] Merz, K. W.; Rauchle, K. Arch. Pharm. 1960, 16, 968.
[27] Okamoto, O.; Kobayashi, K.; Kawamoto, H.; Ito, S.; Satoh, A.; Kato, T.; Yamamoto, I.; Mizutani, S.; Hashimoto, M.; Shimizu, A.; Sakoh, H.; Nagatomi, Y.; Iwasawa, Y.; Takahashi, H.; Ishii, Y.; Ozaki, S.; Ohta, H. Bioorg. Med. Chem. Lett. 2008, 18, 3278.
[28] Baer, J. E.; Lockwood, R. G. J. Org. Chem. 1954, 76, 1162.
[29] Boyd, R. N.; Meadow, M. Anal. Chem. 1960, 32, 551.
[30] Luzzio, F. A. Synth. Commun. 1984, 14, 209.
[31] Finnegan, W. G.; Henry, R. A.; Lieber, E. J. Org. Chem. 1953, 75, 779.
[32] Herbst, R. M.; Roberts, C. W.; Harvill, E. J. J. Org. Chem. 1951, 16, 139.
[33] Rule, N. G.; Detty, M. R.; Kaeding, J. E.; Sinicropi, J. A. J. Org. Chem. 1995, 60, 1665.
[34] Wei, X. C.; Du, Z. Y.; Zheng, X.; Cui, X. X.; Conney, A. H.; Zhang, K. Eur. J. Med. Chem. 2012, 53, 235.
[35] Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353.
[36] Zakharychev, V. V.; Kuzenkov, A. V. Chem. Heterocycl. Compd. 2007, 43, 989.
[37] Wallace, R. J. Jr.; Nash, D. R.; Steele, L. C.; Steingrube, V. J. Clin. Microbiol. 1986, 24, 976.
[38] Liang, G.; Zhou, H.; Wang, Y.; Gurley, E. C.; Feng, B.; Chen, L.; Xiao, J.; Yang, S.; Li, X. J. Cell. Mol. Med. 2009, 13, 3370.
[39] Weber, W. M.; Hunsaker, L. A.; Abcouwer, S. F.; Deck, L. M.; Vanderjagt, L. D. L. Bioorg. Med. Chem. 2005, 13, 3811.
[40] Sato, T.; Ino, H.; Fujitsuka, M.; Tanaka, K. Tetrahedron Lett. 1997, 38, 6039.
[41] Hazarkhani, H. Kumar, P.; Kondiram, K. S.; Shafi, G.; Ikhlas, M. S. G. Synthetic Communications 2010, 40, 2887.
[42] Musumarra, G.; Ballistreri, F. P. Org. Magn. Res. 1980, 14, 384.

Options
文章导航

/

〈 〉