Synthesis and evaluation of novelN;N′-disubstituted benzimidazolium bromidessalts as antitumor agents

Synthesis and evaluation of novelN;N′-disubstituted benzimidazolium bromidessalts as antitumor agents

Novel benzimidazolium bromides salts having (4-methoxyphenyl)ethyl, (phthalimide-2-yl)methyl, 4-nitro-benzyl, 2-phenylethyl, penthyl, or allyl groups were synthesized and their characterizations were conducted by1H and13C NMR and IR spectroscopic methods, and microanalysis. In vitro antitumor activities of the novel benzimidazolecompounds (1{7) were determined by using ovarian (A2780) and prostate (PC-3) cancer cell lines. Antitumor propertiesof all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Atime-dependent cell viability assay for the tested benzimidazole compounds was performed and the IC50values of thecompounds were calculated after treatment for 24 and 48 h. Our results indicate that the tested benzimidazole compoundsshow antitumor activity against A2780 and PC-3 cell lines (P

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  • 1.Li, Z.; Zhang, S.; Deng, L.; Hu, J.; Li, H.; Zhao, Y.; Luo, Y.; Huang, W.Med. Chem. Res.2014,23, 4050-4059.
  • 2.Kamal, A.; Kumar, G. B.; Nayak, V. L.; Reddy, V. S.; Shaik, A. B.; Rajender, R.; Reddy, R. M.Med. Chem.Commun.2015,6, 606-612.
  • 3.Kidwai, M.; Venkataramanan, R.; Mohan, R.; Sapra, P.Curr. Med. Chem.2002,9, 1209-1228.
  • 4.Gulland, A.Brit. Med. J.2014,348: g1338, 1.5.Carlsson, E.; Lindberg, P.; Unge, S.Chem. Britain.2002,38, 42-45.
  • 6.Kaur, N.; Kaur, A.; Bansal, Y.; Shah, D. I.; Bansal, G.; Singh, M.Bioorg. Med. Chem.2008,16, 10210-10215.
  • 7.Morningstar, M. L.; Roth, T.; Farnsworth, D. W.; Smith, M. K.; Watson, K.; Buckheit, R. W.; Das, K.; Zhang,W.; Arnold, E.; Julias, J. G. et al.J. Med. Chem.2007,50, 4003-4015.
  • 8.Alp, M.; Goker, H.; Burun, R.; Yldz, S.Eur. J. Med. Chem.2009,44, 2002-2008.
  • 9.Kucukbay, H.; Durmaz, R.; Okuyucu, N.; Gunal, S.Folia Microbiol.2003,48, 679- 681.
  • 10.Ylmaz,U.; Kucukbay, H.; Sireci, N.; Akkurt, M.; Gunal, S.; Durmaz, R.; Tahir, M. N.Appl. Organomet. Chem.2011,25, 366-373.
  • 11.Camacho, J.; Barazarte, A.; Gamboa, N.; Rodrigues, J.; Rojas, R.; Vaisberg, A.; Gilman, R.; Charris, J.Bioorg.Med. Chem.2008,16, 3661-3674.
  • 12.Abu-Bakr, S. M.; Bassyouni, F. A.; Rehim, M. A.Res. Chem. Intermed.2012,38, 2523-2545.
  • 13.Shah, K.; Chhabra, S.; Shrivastava, S. K.; Mishra, P. Med. Chem. Res.2013,22, 5077-5104.
  • 14.Singla, P.; Luxami, V.; Paul, K.RSC Advances2014,4, 12422-12440.
  • 15.Yurttas, L.; Demirayak, S.; Ciftci, G. A.; Yldrm, S. U.; Kaplanckl, Z. A. Arch. Pharm.2013,346, 403-414.
  • 16.Paul, K.; Bindal, S.; Luxami, V.Bioorg. Med. Chem. Lett.2013,23, 3667-3672.
  • 17.Azam, M.; Khan, A. A.; Al-Resayes, S. I.; Islam, M. S.; Saxena, A. K.; Dwivedi, S.; Musarrat, J.; Kruszynska, A.T.; Kruszynski, R.Spectrochim. Acta A2015,142, 286-291.
  • 18.Xu, X. L.; Yu, C. L.; Chen, W.; Li, Y. C.; Yang, L. J.; Li, Y.; Zhang, H. B.; Yang, X. D.Org. Biomol. Chem.2015,13, 1550-1557.
  • 19.Rodionov, A. N.; Zherebker, K. Y.; Snegur, L. V.; Korlyukov, A. A.; Arhipov, D. E.; Peregudov, A. S.; Ilyin, M.M.; Nikitin, O. M.; Morozova, N. B.; Simenel, A. A.J. Organomet. Chem.2015,783, 83-91.
  • 20.Sharma, A.; Luxami, V.; Paul, K.Eur. J. Med. Chem.2015,93, 414-422.
  • 21.Gao, C.; Li, B.; Zhang, B.; Sun, Q.; Li, L.; Li, X.; Chen, C.; Tan, C.; Liu, H.; Jiang, Y.Bioorg. Med. Chem.2015,23, 1800 -1807.
  • 22.Singla, P.; Luxami, V.; Paul, K.Bioorg. Med. Chem.2015,23, 1691-1700.
  • 23.Hu, Z.; Ou, L.; Li, S.; Yang, L.Med. Chem. Res.2014,23, 3029-3038.
  • 24.Paul, K.; Sharma, A.; Luxami, V.Bioorg. Med. Chem. Lett.2014,24, 624-629.
  • 25.Shao, K. P.; Zhang, X. Y.; Chen, P. J.; Xue, D. Q.; He, P.; Ma, L. Y.; Zheng, J. X.; Zhang, Q. R.; Liu, H. M.Bioorg. Med. Chem. Lett.2014,24, 3877-3881.
  • 26.Lukevics, E.; Arsenyan, P.; Shestakova, I.; Domracheva, I.; Nesterova, A.; Pudova, O.Eur. J. Med. Chem.2001,36, 507-515.
  • 27.Kucukbay, H.; Ylmaz,U.; Sireci, N.;Onganer, A. N.Turk. J. Chem.2011,35, 561-571.
  • 28.Kucukbay, H.; Durmaz, R.; Okuyucu, N.; Gunal, S.; Kazaz, C.Arzneim.-Forsch./Drug Res.2004,54, 64-68.
  • 29.Kucukbay, H.; Durmaz, R.; Guven, M.; Gunal, S.Arzneim.-Forsch./Drug Res.2001,51, 420-424.
  • 30.Durmaz, R.; Koroglu, M.; Kucukbay, H.; Temel,_I.;Ozer, M. K.; Re q, M.; Cetinkaya, E.; Cetinkaya, B.; Yologlu,S.Arzneim.-Forsch./Drug Res.1998,48, 1179-1184.
  • 31.Kucukbay, H.; Durmaz, B.Arzneim.-Forsch./Drug Res.1997,47, 667-670.
  • 32.Cetinkaya, B.; Cetinkaya, E.; Kucukbay, H.; Durmaz, R.Arzneim.-Forsch./Drug Res.1996,46, 1154-1158.
  • 33.Cetinkaya, B.; Cetinkaya, E.; Kucukbay, H.; Durmaz, R.Arzneim.-Forsch./Drug Res.1996,46, 821-823.
  • 34.Kucukkbay, H.; Cetinkaya, E., Durmaz, R.Arzneim.-Forsch./Drug Res.1995,45, 1331-1334.
  • 35.Kucukbay, H.; Sireci, N.; Ylmaz,U.; Akkurt, M.; Yalcn, S. P.; Tahir, M. N.; Ott, H.Appl. Organomet. Chem.2011,25, 255-261.
  • 36.Li, C. J.; Chen, L.Chem. Rev.2006,35, 68-82.
  • 37.Phillips, M. A.J. Chem. Soc.1928,13, 2393-2399.
  • 38.Mumcu, A. Kucukbay, H.Magn. Reson. Chem.2015,53, 1024-1030.
  • 39.Kolocouris, N.; Foscolos, G. B.; Kolocouris, A.; Marakos, P.; Pouli, N.; Fytas, G.; Ikeda, S.; DeClercq, E.J. Med.Chem.1994,37, 2896-2902.
  • 40.Gorgulu, A. O.; Koran, K.;Ozen, F.; Tekin, S.; Sandal, S.J. Mol. Struct.2015,1087, 1-10.41.Mosamann, T. R.; Cherwinski, H.; Bond, M. V.; Giedlin, M. A.; Coffmann, R. F.J.Immunol.1986,136, 2348-2357.
Turkish Journal of Chemistry-Cover
  • ISSN: 1300-0527
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK