Chinese Journal of Organic Chemistry >
Synthesis and in vitro Anticancer Activity of N-Methylisoxazolinium-Salts with Carboxyl or Ester Groups against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase-1
Received date: 2016-04-15
Revised date: 2016-07-12
Online published: 2016-09-06
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21462043, 21062019).
Fouteen 2-methyl-3-ethylcarboxy-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino[3',4'-d]-isoxazoliniumtetrachloro-ferrate derivatives 2a~2g and 2-methyl-3-carboxyl-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino[3',4'-d]-isoxazolinium-tetra-chloroferrate derivatives 4a~4g were synthesized by using dimethylsulfate as a N-methylating reagent and ferric(III)-chloride as anion exchange reagent in hydrochloric acid. The structures of the target compounds 2 and 4 were characterized by 1H NMR, IR spectra and elemental analysis. The preliminary in vitro anticancer activity on the compounds showed that most compounds possess anti-cancer activity at some extent. At the test concentration of 20 μg/mL, compounds 2a~2g and 4a~4g showed inhibition activities in the range of 97.32%~99.94% and 97.45%~99.92% against cell division cycle 25B phosphatase (Cdc25B), respectively. At the test concentration of 20 μg/mL, compounds 2a~2g and 4d~4g showed inhibition activities in the range of 52.18%~97.15% and 86.66%~99.45% against SH2-containing protein tyrosine phosphatase-1 (SHP1), respectively. Compounds 4a~4c only have the inhibition activities in the range of 15.21%~47.11%, which is lower than IC50 against SHP1. Preliminary discussion was carried out on the structure-activity relationship of the target compounds.
Imerhasan Mukhtar, Helil Setiwaldi, Mahmud Muhammed Amin . Synthesis and in vitro Anticancer Activity of N-Methylisoxazolinium-Salts with Carboxyl or Ester Groups against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase-1[J]. Chinese Journal of Organic Chemistry, 2017 , 37(2) : 496 -502 . DOI: 10.6023/cjoc201604033
[1] Jäger, V.; Colinas, P. A. In Synthetic Applications of 1,3-Dipolar Cycloaddtion Chemistry toward Heterocycles and Natural Products, Vol. 59, Eds.: Padwa, A.; Pearson, W. H., John Wiley & Sons, Inc., New York, 2002, pp. 361~472.
[2] Jaeger, V.; Grund, H.; Buss, W. Bull. Soc. Chem. Belg. 1983, 92, 1039.
[3] Henneböhle, M.; LeRoy, P. Y.; Jäger, V. Z. Naturforsch. 2004, 59B, 451.
[4] Frey, W.; Imerhasan, M.; Bathich, Y.; Jäger, V. Z. Kristallogr.-New Cryst. Struct. 2005, 220, 151.
[5] Bathich, Y.; Imerhasan, M.; Jäger, V. The 6th Iminiumsalz-Tagung (ImSaT-6), Stimpfach-Rechenberg, Germany, 2003, pp. 99~107.
[6] Bathich, Y.; Henneböhle, M.; LeRoy, P. Y.; Imerhasan, M.; Jäger, V. Organische Chemie, Bad Nauheim, Germany, 2004, pp. 220~227.
[7] Frey, W.; Henneböhle, M.; Jäger, V. Z. Kristallogr.-New Cryst. Struct. 2005, 220, 149.
[8] Jäger, V.; Bathich, Y.; Shiva, S.; Li, F.; Ibrahim, M.; Henneböhle, M.; LeRoy, P. Y.; Imerhasan, M. 2nd International Conference on Heterocyclic Chemistry, University of Rajasthan, Jaipur India, 2006, pp. 1~15.
[9] Llamas, K,; Owens, M.; Blakeley, R. L.; Zerner, B. J. Am. Chem. Soc. 1986, 108, 5543.
[10] Kohler, E. P.; Blatt, A. H. J. Am. Chem. Soc. 1928, 50, 1217.
[11] Kohler, E. P.; Bruce, W. F. J. Am. Chem. Soc. 1931, 53, 644.
[12] Bodlaender, P.; Feinstein, G.; Shaw, E. Biochemistry 1969, 8, 4941.
[13] Ali, T.; Imerhasan, M.; Hudabergen, A. Chin. J. Org. Chem. 2012, 32, 376 (in Chinese).(图尔麦麦提·艾力, 穆赫塔尔·伊米尔艾, 阿依努尔·胡达依别尔根, 有机化学, 2012, 32, 376.)
[14] Li, J.-M.; Wang, J.; Liu, H.; Guo, J.-W.; Zuo, L.-F. Chin. J. Tumor 2008, 28, 586 (in Chinese).(李金梅, 王静, 刘辉, 刘江惠, 郭建文, 左连富, 肿瘤, 2008, 28, 586.)
[15] Pagel, J. M.; Appelbaum, F. R.; Eary, J. F.; Rajendran, J.; Fisher, D. R.; Gooley, T.; Ruffner, K.; Nemecek, E.; Sickle, E.; Durack, L.; Carreras, J.; Horowitz, M. M.; Press, O. W.; Gopal, A. K.; Martin, P. J.; Bernstein, I. D.; Matthews, D. C. Blood 2006, 107, 2184.
[16] Imerhasan, M.; Osman, K.; Muhammad, T.; Helil, S.; Haydar, G. Chin. J. Appl. Chem. 2008, 25, 931 (in Chinese).(穆赫塔尔·伊米尔艾山, 库尔班·吾斯曼, 吐尔洪·买买提, 萨提瓦尔迪·海力力, 古丽伯斯坦·阿依达尔, 应用化学, 2008, 25, 931.)
[17] Kristjansdottir, K.; Rudolph, J. Chem. Biol. 2004, 11, 1043.
/
| 〈 |
|
〉 |
