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Synthesis and biological evaluation of N-hydroxybenzimidazoles as potential anticancer agents targeting human lactate dehydrogenase A

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Abstract

In this paper, a novel series of N-hydroxybenzimidazoles as potential anticancer agents were designed and synthesized. The in vitro enzymatic assays suggested N-hydroxy-6-(3-nitrophenyl)-benzimidazole-2-carboxylic acid had good inhibitory potency (IC50 = 0.25 μM) to human lactate dehydrogenase A. Cytotoxic assay revealed that this compound gave the best potency (IC50 = 2.2 μM) to inhibit BGC-823 cell proliferation. Furthermore, molecular docking study showed it had strong interactions with lactate dehydrogenase A, which was in line with our experimental results.

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References

  1. Descoteaux C, Brasseur K, Leblanc V, Parent S, Asselin E, Berube G (2012) Amino Acids 43:923

    Article  CAS  Google Scholar 

  2. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing XJ, Lonigro RJ, Brenner JC, Asangani IA, Ateeq B, Chun SY, Siddiqui J, Sam L, Anstett M, Mehra R, Prensner JR, Palanisamy N, Ryslik GA, Vandin F, Raphael BJ, Kunju Lakshmi P, Rhodes DR, Pienta KJ, Chinnaiyan AM, Tomlins SA (2012) Nature 487:239

    Article  CAS  Google Scholar 

  3. Warburg O (1956) Science 123:309

    Article  CAS  Google Scholar 

  4. Kroemer G, Pouyssegur J (2008) Cancer Cell 13:472

    Article  CAS  Google Scholar 

  5. Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmel AB, Rich JN (2010) Br J Cancer 102:789

    Article  CAS  Google Scholar 

  6. Shroff GK, Kuna R, Dirsipam K, Yalagala R, Mitra P (2011) Anti Cancer Agents Med Chem 11:272

    Article  CAS  Google Scholar 

  7. Price GS, Page RL, Riviere JE, Cline JM, Thrall DE (1996) Cancer Chemother Pharmacol 38:129

    Article  CAS  Google Scholar 

  8. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED (2007) Cancer Cell 11:37

    Article  CAS  Google Scholar 

  9. Labadie S, Dragovich PS, Chen J, Fauber BP, Boggs J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Ho Q, Lai KW, Ma S, Malek S, Peterson D, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou AH (2015) Bioorg Med Chem Lett 25:75

    Article  CAS  Google Scholar 

  10. Granchi C, Roy S, Mottinelli M, Nardini E, Campinoti F, Tuccinardi T, Lanza M, Betti L, Giannaccini G, Lucacchini A, Martinelli A, Macchia M, Minutolo F (2011) Bioorg Med Chem Lett 21:7331

    Article  CAS  Google Scholar 

  11. Dragovich PS, Fauber BP, Corson LB, Ding CZ, Eigenbrot C, Ge H, Giannetti AM, Hunsaker T, Labadie S, Liu Y, Malek S, Pan B, Peterson D, Pitts K, Purkey HE, Sideris S, Ultsch M, VanderPorten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X (2013) Bioorg Med Chem Lett 23:3186

    Article  CAS  Google Scholar 

  12. Fauber BP, Dragovich PS, Chen J, Corson LB, Ding CZ, Eigenbrot C, Giannetti AM, Hunsaker T, Labadie S, Liu Y, Liu Y, Malek S, Peterson D, Pitts K, Sideris S, Ultsch M, VanderPorten E, Wang J, Wei B, Yen I, Yue Q (2013) Bioorg Med Chem Lett 23:5533

    Article  CAS  Google Scholar 

  13. Dragovich PS, Fauber BP, Boggs J, Chen J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Giannetti AM, Hunsaker T, Labadie S, Li C, Liu Y, Liu Y, Ma S, Malek S, Peterson D, Pitts KE, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wang J, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou AH (2014) Bioorg Med Chem Lett 24:3764

    Article  CAS  Google Scholar 

  14. Granchi C, Bertini S, Macchia M, Minutolo F (2010) Curr Med Chem 17:672

    Article  CAS  Google Scholar 

  15. Choi SR, Pradhan A, Hammond NL, Chittiboyina AG, Tekwani BL, Avery MA (2007) J Med Chem 50:3841

    Article  CAS  Google Scholar 

  16. Granchi C, Roy S, Giacomelli C, Macchia M, Tuccinardi T, Martinelli A, Lanza M, Betti L, Giannaccini G, Lucacchini A, Funel N, León LG, Giovannetti E, Peters GJ, Palchaudhuri R, Calvaresi EC, Hergenrother PJ, Minutolo F (2011) J Med Chem 54:1599

    Article  CAS  Google Scholar 

  17. Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, Whittaker D, Wingfield J, Winter J, Hudson K (2012) J Med Chem 55:3285

    Article  CAS  Google Scholar 

  18. Kohlmann A, Zech SG, Li F, Zhou T, Squillace RM, Commodore L, Greenfield MT, Lu X, Miller DP, Huang WS, Qi J, Thomas RM, Wang Y, Zhang S, Dodd R, Liu S, Xu R, Xu Y, Miret JJ, Rivera V, Clackson T, Shakespeare WC, Zhu X, Dalgarno DC (2013) J Med Chem 56:1023

    Article  CAS  Google Scholar 

  19. Granchi C, Roy S, Fiandra CD, Tuccinardi T, Lanza M, Betti L, Giannaccini G, Lucacchini A, Martinelli A, Macchia M, Minutolo F (2011) Med Chem Commun 2:638

    Article  CAS  Google Scholar 

  20. Wang Z, Wang D, Han S, Wang N, Mo F, Loo TY, Shen J, Huang H, Chen J (2013) PLoS ONE 8:e56631

    Article  CAS  Google Scholar 

  21. Shi Y, Pinto BM (2014) PLoS ONE 9:e86365

    Article  Google Scholar 

  22. Augoff K, Hryniewicz-Jankowska A, Tabola R (2015) Cancer Lett 358:1

    Article  CAS  Google Scholar 

  23. Thornburg JM, Nelson KK, Clem BF, Lane AN, Arumugam S, Simmons A, Eaton JW, Telang S, Chesney J (2008) Breast Cancer Res 10:R84

    Article  Google Scholar 

  24. Cameron A, Read J, Tranter R, Winter VJ, Sessions RB, Brady RL, Vivas L, Easton A, Kendrick H, Croft SL, Barros D, Lavandera JL, Martin JJ, Risco F, García-Ochoa S, Gamo FJ, Sanz L, Leon L, Ruiz JR, Gabarró R, Mallo A, Gómez de las HF (2004) J Biol Chem 279:31429

    Article  CAS  Google Scholar 

  25. Tong YS, Bouska JJ, Ellis PA, Johnson EF, Leverson J, Liu XS, Marcotte PA, Olson AM, Osterling DJ, Przytulinska M, Rodriguez LE, Shi Y, Soni N, Stavropoulos J, Thomas S, Donawho CK, Frost DJ, Luo Y, Giranda VL, Penning TD (2009) J Med Chem 52:6803

    Article  CAS  Google Scholar 

  26. Sann CL, Baron A, Mann J, Berg HVD, Gunaratnam M, Neidle S (2006) Org Biomol Chem 4:1305

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Information, Shandong Jining No. 1 People’s Hospital, Jining, 272002, China

    Wei Yue

  2. Hong-Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, 710054, China

    Hu Wang

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  1. Wei Yue
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  2. Hu Wang
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Correspondence to Hu Wang.

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Yue, W., Wang, H. Synthesis and biological evaluation of N-hydroxybenzimidazoles as potential anticancer agents targeting human lactate dehydrogenase A. Monatsh Chem 146, 2079–2086 (2015). https://doi.org/10.1007/s00706-015-1513-9

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  • DOI: https://doi.org/10.1007/s00706-015-1513-9

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