Advertisement

Science China Chemistry

, Volume 61, Issue 5, pp 557–568 | Cite as

Discovery of natural berberine-derived nitroimidazoles as potentially multi-targeting agents against drug-resistant Escherichia coli

  • Guo-Biao Zhang
  • Swetha Kameswari Maddili
  • Vijai Kumar Reddy Tangadanchu
  • Lavanya Gopala
  • Wei-Wei Gao
  • Gui-Xin CaiEmail author
  • Cheng-He ZhouEmail author
Articles

Abstract

A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance (NMR), infrared spectra (IR), and high resolution mass spectra (HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative 8f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration (MIC) value of 0.003 mM, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and ClogP values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8f could also selectively address resistant E. coli from a mixture of various strains.

Keywords

berberine nitroimidazole Escherichia coli DNA membrane permeabilization 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

This work was partially supported by the National Natural Science Foundation of China (21672173, 21372186), Research Fund for International Young Scientists from International (Regional) Cooperation and Exchange Program of NSFC (81650110529), Chongqing Special Foundation for Postdoctoral Research Proposal (Xm2016039, Xm2017185), Program for Overseas Young Talents from State Administration of Foreign Experts Affairs, China (WQ2017XNDX047), the Doctoral Fund of Southwest University (SWU111075), and the Research Funds for the Central Universities (XDJK2017B015).

Supplementary material

11426_2017_9169_MOESM1_ESM.pdf (2.3 mb)
Discovery of Natural Berberine-derived Nitroimidazoles as Potentially Multi-targeting Agents against Drug-resistant Escherichia coli

References

  1. 1.
    Garland M, Loscher S, Bogyo M. Chem Rev, 2017, 117: 4422–4461CrossRefGoogle Scholar
  2. 2.
    Brown ED, Wright GD. Nature, 2016, 529: 336–343CrossRefGoogle Scholar
  3. 3 (a).
    Petty NK, Ben Zakour NL, Stanton-Cook M, Skippington E, Totsika M, Forde BM, Phan MD, Gomes Moriel D, Peters KM, Davies M, Rogers BA, Dougan G, Rodriguez-Baño J, Pascual A, Pitout JDD, Upton M, Paterson DL, Walsh TR, Schembri MA, Beatson SA. Proc Natl Acad Sci USA, 2014, 111: 5694–5699CrossRefGoogle Scholar
  4. (b).
    Guo Y, Liu X, Li B, Yao J, Wood TK, Wang X. J Bacteriol, 2017, 199: e00057CrossRefGoogle Scholar
  5. 4 (a).
    Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K. Nature, 2015, 517: 455–459CrossRefGoogle Scholar
  6. (b).
    O’Connell KMG, Hodgkinson JT, Sore HF, Welch M, Salmond GPC, Spring DR. Angew Chem Int Ed, 2013, 52: 10706–10733CrossRefGoogle Scholar
  7. 5 (a).
    Peng XM, Damu GLV, Zhou CH. Curr Pharm Des, 2013, 19: 3884–3930CrossRefGoogle Scholar
  8. (b).
    Silva LN, Zimmer KR, Macedo AJ, Trentin DS. Chem Rev, 2016, 116: 9162–9236CrossRefGoogle Scholar
  9. 6.
    Tillhon M, Guamán Ortiz LM, Lombardi P, Scovassi AI. Biochem Pharmacol, 2012, 84: 1260–1267CrossRefGoogle Scholar
  10. 7 (a).
    Jeyakkumar P, Zhang L, Avula SR, Zhou CH. Eur J Med Chem, 2016, 122: 205–215CrossRefGoogle Scholar
  11. (b).
    Mistry B, Keum YS, Noorzai R, Gansukh E, Kim DH. J Iran Chem Soc, 2016, 13: 531–539CrossRefGoogle Scholar
  12. 8 (a).
    Endeshaw M, Zhu X, He S, Pandharkar T, Cason E, Mahasenan KV, Agarwal H, Li C, Munde M, Wilson WD, Bahar M, Doskotch RW, Kinghorn AD, Kaiser M, Brun R, Drew ME, Werbovetz KA. J Nat Prod, 2013, 76: 311–315CrossRefGoogle Scholar
  13. (b).
    Kumar A, Ekavali A, Chopra K, Mukherjee M, Pottabathini R, Dhull DK. Eur J Pharmacol, 2015, 761: 288–297CrossRefGoogle Scholar
  14. 9.
    Duan JR, Liu HB, Jeyakkumar P, Gopala L, Li S, Geng RX, Zhou CH. Med Chem Commun, 2017, 8: 907–916CrossRefGoogle Scholar
  15. 10 (a).
    Peng XM, Cai GX, Zhou CH. Curr Top Med Chem, 2013, 13: 1963–2010CrossRefGoogle Scholar
  16. (b).
    Zhang HZ, Gan LL, Wang H, Zhou CH. Mini-Rev Med Chem, 2017, 17: 122–166CrossRefGoogle Scholar
  17. (c).
    Liu HB, Gao WW, Tangadanchu VKR, Zhou CH, Geng RX. Eur J Med Chem, 2018, 143: 66–84CrossRefGoogle Scholar
  18. 11.
    Khalaj A, Nakhjiri M, Negahbani AS, Samadizadeh M, Firoozpour L, Rajabalian S, Samadi N, Faramarzi MA, Adibpour N, Shafiee A, Foroumadi A. Eur J Med Chem, 2011, 46: 65–70CrossRefGoogle Scholar
  19. 12.
    Ang CW, Jarrad AM, Cooper MA, Blaskovich MAT. J Med Chem, 2017, 60: 7636–7657CrossRefGoogle Scholar
  20. 13.
    Cui SF, Peng LP, Zhang HZ, Rasheed S, Vijaya Kumar K, Zhou CH. Eur J Med Chem, 2014, 86: 318–334CrossRefGoogle Scholar
  21. 14 (a).
    Zhang L, Peng XM, Damu GLV, Geng RX, Zhou CH. Med Res Rev, 2014, 34: 340–437CrossRefGoogle Scholar
  22. (b).
    Rouf A, Tanyeli C. Eur J Med Chem, 2015, 97: 911–927CrossRefGoogle Scholar
  23. (c).
    Zhou CH, Wang Y. Curr Med Chem, 2012, 19: 239–280CrossRefGoogle Scholar
  24. (d).
    Dai L, Cui S, Damu GLV, Zhou C. Chin J Org Chem, 2013, 33: 224–244CrossRefGoogle Scholar
  25. 15.
    Zhang SL, Chang JJ, Damu GLV, Fang B, Zhou XD, Geng RX, Zhou CH. Bioorg Med Chem Lett, 2013, 23: 1008–1012CrossRefGoogle Scholar
  26. 16.
    Wen SQ, Jeyakkumar P, Avula SR, Zhang L, Zhou CH. Bioorg Med Chem Lett, 2016, 26: 2768–2773CrossRefGoogle Scholar
  27. 17 (a).
    Jeyakkumar P, Liu HB, Gopala L, Cheng Y, Peng XM, Geng RX, Zhou CH. Bioorg Med Chem Lett, 2017, 27: 1737–1743CrossRefGoogle Scholar
  28. (b).
    Lai TT, Xie D, Zhou CH, Cai GX. J Org Chem, 2016, 81: 8806–8815CrossRefGoogle Scholar
  29. 18 (a).
    Zhang FF, Gan LL, Zhou CH. Bioorg Med Chem Lett, 2010, 20: 1881–1884CrossRefGoogle Scholar
  30. (b).
    Peng XM, Kumar KV, Damu GLV, Zhou CH. Sci China Chem, 2016, 59: 878–894CrossRefGoogle Scholar
  31. 19 (a).
    Su T, Xie S, Wei H, Yan J, Huang L, Li X. Bioorg Med Chem, 2013, 21: 5830–5840CrossRefGoogle Scholar
  32. (b).
    Zhang L, Chang JJ, Zhang SL, Damu GLV, Geng RX, Zhou CH. Bioorg Med Chem, 2013, 21: 4158–4169CrossRefGoogle Scholar
  33. 20.
    Salas PF, Herrmann C, Cawthray JF, Nimphius C, Kenkel A, Chen J, de Kock C, Smith PJ, Patrick BO, Adam MJ, Orvig C. J Med Chem, 2013, 56: 1596–1613CrossRefGoogle Scholar
  34. 21 (a).
    Zelikin AN, Ehrhardt C, Healy AM. Nat Chem, 2016, 8: 997–1007CrossRefGoogle Scholar
  35. (b).
    Dai LL, Zhang HZ, Nagarajan S, Rasheed S, Zhou CH. Med Chem Commun, 2015, 6: 147–154CrossRefGoogle Scholar
  36. 22 (a).
    von Karstedt S, Montinaro A, Walczak H. Nat Rev Cancer, 2017, 17: 352–366CrossRefGoogle Scholar
  37. (b).
    Cui SF, Addla D, Zhou CH. J Med Chem, 2016, 59: 4488–4510CrossRefGoogle Scholar
  38. 23 (a).
    Wolny-Koladka K, Lenart-Boron A. Water Air Soil Pollut, 2016, 227: 146CrossRefGoogle Scholar
  39. (b).
    Hu J, Liu F, Ju H. Angew Chem Int Ed, 2016, 55: 6667–6670CrossRefGoogle Scholar
  40. 24 (a).
    Konai MM, Ghosh C, Yarlagadda V, Samaddar S, Haldar J. J Med Chem, 2014, 57: 9409–9423CrossRefGoogle Scholar
  41. (b).
    Gao WW, Zhou CH. Future Med Chem, 2017, 9: 1461–1464CrossRefGoogle Scholar
  42. 25 (a).
    Abraham CS, Prasana JC, Muthu S. Spectrochim Acta A, 2017, 181: 153–163CrossRefGoogle Scholar
  43. (b).
    Dey T, Praveena KSS, Pal S, Mukherjee AK. J Mol Struct, 2017, 1137: 615–625CrossRefGoogle Scholar
  44. 26.
    Cheng Y, Avula SR, Gao WW, Addla D, Tangadanchu VKR, Zhang L, Lin JM, Zhou CH. Eur J Med Chem, 2016, 124: 935–945CrossRefGoogle Scholar
  45. 27.
    Zhang HZ, He SC, Peng YJ, Zhang HJ, Gopala L, Tangadanchu VKR, Gan LL, Zhou CH. Eur J Med Chem, 2017, 136: 165–183CrossRefGoogle Scholar
  46. 28.
    Gao WW, Rasheed S, Tangadanchu VKR, Sun Y, Peng XM, Cheng Y, Zhang FX, Lin JM, Zhou CH. Sci China Chem, 2017, 60: 769–785CrossRefGoogle Scholar
  47. 29 (a).
    Zhang SL, Chang JJ, Damu GLV, Geng RX, Zhou CH. Med Chem Commun, 2013, 4: 839–846CrossRefGoogle Scholar
  48. (b).
    Yin BT, Yan CY, Peng XM, Zhang SL, Rasheed S, Geng RX, Zhou CH. Eur J Med Chem, 2014, 71: 148–159CrossRefGoogle Scholar
  49. (c).
    Fang XF, Li D, Tangadanchu VKR, Gopala L, Gao WW, Zhou CH. Bioorg Med Chem Lett, 2017, 27: 4964–4969CrossRefGoogle Scholar
  50. 30 (a).
    Shimazaki Y, Tanaka J, Kohara Y, Kamahori M, Sakamoto T. Anal Chem, 2017, 89: 6305–6308CrossRefGoogle Scholar
  51. (b).
    Addla D, Wen SQ, Gao WW, Maddili SK, Zhang L, Zhou CH. Med Chem Commun, 2016, 7: 1988–1994CrossRefGoogle Scholar
  52. 31.
    Jiang H, Wang X, Huang L, Luo Z, Su T, Ding K, Li X. Bioorg Med Chem, 2011, 19: 7228–7235CrossRefGoogle Scholar
  53. 32 (a).
    Peng LP, Nagarajan S, Rasheed S, Zhou CH. Med Chem Commun, 2015, 6: 222–229CrossRefGoogle Scholar
  54. (b).
    Zhang L, Kumar KV, Rasheed S, Zhang SL, Geng RX, Zhou CH. Med Chem Commun, 2015, 6: 1303–1310CrossRefGoogle Scholar
  55. (c).
    Li ZZ, Gopala L, Tangadanchu VKR, Gao WW, Zhou CH. Bioorg Med Chem, 2017, 25: 6511–6522CrossRefGoogle Scholar
  56. 33.
    Zhang Y, Damu GLV, Cui SF, Mi JL, Tangadanchu VKR, Zhou CH. Med Chem Commun, 2017, 8: 1631–1639CrossRefGoogle Scholar
  57. 34.
    Zhang L, Addla D, Ponmani J, Wang A, Xie D, Wang YN, Zhang SL, Geng RX, Cai GX, Li S, Zhou CH. Eur J Med Chem, 2016, 111: 160–182CrossRefGoogle Scholar
  58. 35.
    Velema WA, van der Berg JP, Szymanski W, Driessen AJM, Feringa BL. ACS Chem Biol, 2014, 9: 1969–1974CrossRefGoogle Scholar
  59. 36.
    Zheng T, Nolan EM. J Am Chem Soc, 2014, 136: 9677–9691CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Guo-Biao Zhang
    • 1
  • Swetha Kameswari Maddili
    • 1
  • Vijai Kumar Reddy Tangadanchu
    • 1
  • Lavanya Gopala
    • 1
  • Wei-Wei Gao
    • 1
  • Gui-Xin Cai
    • 1
    Email author
  • Cheng-He Zhou
    • 1
    Email author
  1. 1.Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical EngineeringSouthwest UniversityChongqingChina

Personalised recommendations