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A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

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Abstract

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-1,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.

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References

  1. Zhang YY, Mi JL, Zhou CH, Zhou XD. Synthesis of novel fluconazoliums and their evaluation for antibacterial and antifungal activities. Eur J Med Chem, 2011, 46: 4391–4402

    Article  CAS  Google Scholar 

  2. Sk UH, Gowda ASP, Crampsie MA, Yun JK, Spratt TE, Amin S, Sharma AK. Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics. Eur J Med Chem, 2011, 46: 3331–3338

    Article  CAS  Google Scholar 

  3. Hariprakasha HK, Kosakowska-Cholody T, Meyer C, Cholody WM, Stinson SF, Tarasova NI, Michejda CJ. Optimization of naphthalimide-imidazoacridone with potent antitumor activity leading to clinical candidate (HKH40A, RTA 502). J Med Chem, 2007, 50: 5557–5560

    Article  CAS  Google Scholar 

  4. Quang DT, Kim JS, Fluoro- and chromogenic chemodosimeters for heavy metal ion detection in solution and biospecimens. Chem Rev, 2010, 110: 6280–6301

    Article  CAS  Google Scholar 

  5. Jiang J, Jiang H, Liu W, Tang XL, Zhou X, Liu WS, Liu RT, Liu RT, A colorimetric and ratiometric fluorescent probe for palladium. Org Lett, 2011, 13: 4922–4925

    Article  CAS  Google Scholar 

  6. Qu DH, Wang QC, Ren J, Tian H. A light-driven rotaxane molecular shuttle with dual fluorescence addresses. Org Lett, 2004, 6: 2085–2088

    Article  CAS  Google Scholar 

  7. Felorzabihi N, Froimowicz P, Haley JC, Bardajee GR, Li B, Bovero E, Van Veggel FCJM, Winnik MA. Determination of the Förster distance in polymer films by fluorescence decay for donor dyes with a nonexponential decay profile. J Phys Chem B, 2009, 113: 2262–2272

    Article  CAS  Google Scholar 

  8. Konstantinova TN, Miladinova PM. Synthesis and properties of some fluorescent 1,8-naphthalimide derivatives and their copolymers with methyl methacrylate. J Appl Polym Sci, 2009, 111: 1991–1998

    Article  CAS  Google Scholar 

  9. Li XL, Lin YJ, Wang QQ, Yuan YK, Zhang H, Qian XH. The novel anti-tumor agents of 4-triazol-1,8-naphthalimides: synthesis, cytotoxicity, DNA intercalation and photocleavage. Eur J Med Chem, 2011, 46: 1274–1279

    Article  CAS  Google Scholar 

  10. Farrera-Sinfreu J, Aviñó A, Navarro I, Aymamí J, Beteta NG, Varón S, Pérez-Tomás R, Castillo-Avila W, Eritja R, Albericio F, Royoa M. Design, synthesis and antiproliferative properties of oligomers with chromophore units linked by amide backbones. Bioorg Med Chem Lett, 2008, 18: 2440–2444

    Article  CAS  Google Scholar 

  11. Tian ZY, Xie SQ, Du YW, Ma YF, Zhao J, Gao WY, Wang CJ. Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents. Eur J Med Chem, 2009, 44: 393–399

    Article  CAS  Google Scholar 

  12. Turgeon Z, White D, Jørgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett, 2009, 300: 97–106

    Article  CAS  Google Scholar 

  13. Mohammadkhodaei Z, Mokhtari J, Nouri M. Novel anti-bacterial acid dyes derived from naphthalimide: Synthesis, characterisation and evaluation of their technical properties on nylon 6. Color Technol, 2010, 126: 81–85

    Article  CAS  Google Scholar 

  14. Muth M, Hoerr V, Glaser M, Ponte-Sucre A, Moll H, Stich A, Holzgrabe U. Antitrypanosomal activity of quaternary naphthalimide derivatives. Bioorg Med Chem Lett, 2007, 17: 1590–1593

    Article  CAS  Google Scholar 

  15. Andricopulo AD, Filho VC, Cani GS, Roos JF, Santos ARS, Yunes RA. Analgesic activity of cyclic imides: 1,8-naphthalimide and 1,4,5,8-naphthalenediimide derivatives. Il Farmaco, 2000, 55: 319–321

    Article  CAS  Google Scholar 

  16. Hossain SU, Sengupta S, Bhattacharya S. Synthesis and evaluation of antioxidative properties of a series of organoselenium compounds. Bioorg Med Chem, 2005, 13: 5750–5758

    Article  CAS  Google Scholar 

  17. Kamal A, Ramu R, Tekumalla V, Khanna GBR, Barkume MS, Juvekar AS, Zingde SM. Remarkable DNA binding affinity and potential anticancer activity of pyrrolo[2,1-c][1,4] benzodiazepine-naphthalimide conjugates linked through piperazine side-armed alkane spacers. Bioorg Med Chem, 2008, 16: 7218–7224

    Article  CAS  Google Scholar 

  18. Braña MF, Cacho M, García MA, Pascual-Teresa B, Ramos A, Domínguez MT, Pozuelo JM, Abradelo C, Rey-Stolle MF, Yuste M, Báñez-Coronel M, Lacal JC. New analogues of amonafide and elinafide, containing aromatic heterocycles: Synthesis, antitumor activity, molecular modeling, and DNA binding properties. J Med Chem, 2004, 47: 1391–1399

    Article  Google Scholar 

  19. Filosa R, Peduto A, Micco SD, Caprariis P, Festa M, Petrella A, Capranico G, Bifulco G. synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors. Bioorg Med Chem, 2009, 17: 13–24

    Article  CAS  Google Scholar 

  20. Kamal A, Satyanarayana M, Devaiah V, Rohini V, Yadav JS, Mullick B, Nagaraja V. Synthesis and biological evaluation of coumarin linked fluoroquinolones, phthalimides and naphthalimides as potential DNA gyrase inhibitors. Lett Drug Des Discov, 2006, 3: 494–502

    Article  CAS  Google Scholar 

  21. Zhou CH, Wang Y. Recent researches in triazole compounds as medicinal drugs. Curr Med Chem, 2012, 19: 239–280

    Article  CAS  Google Scholar 

  22. Guillon R, Pagniez F, Rambaud C, Picot C, Duflos M, Logé C, Pape PL. synthesis, and biological evaluation of 1-[(biarylmethyl)-methylamino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl) propan-2-ols as potent antifungal agents: new insights into structure-activity relationships. ChemMedChem, 2011, 6: 1806–1815

    Article  CAS  Google Scholar 

  23. Johnson E, Espinel-Ingroff A, Szekely A, Hockey H, Troke P. Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies. Int J Antimicrob Agents, 2008, 32: 511–514

    Article  CAS  Google Scholar 

  24. Brown ED, Wright GD. New targets and screening approaches in antimicrobial drug discovery. Chem Rev, 2005, 105: 759–774

    Article  CAS  Google Scholar 

  25. Wang XL, Wan K, Zhou CH. Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities. Eur J Med Chem, 2010, 45: 4631–4639

    Article  CAS  Google Scholar 

  26. Zhang YY, Zhou CH. Synthesis and activities of naphthalimide azoles as a new type of antibacterial and antifungal agents. Bioorg Med Chem Lett, 2011, 21: 4349–4352

    Article  CAS  Google Scholar 

  27. Wang Y, Damu GLV, Lv JS, Geng RX, Yang DC, Zhou CH. Design, synthesis and evaluation of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents. Bioorg Med Chem Lett, 2012, 22: 5363–5366

    Article  CAS  Google Scholar 

  28. Shi Y, Zhou CH. Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents. Bioorg Med Chem Lett, 2011, 21: 956–960

    Article  CAS  Google Scholar 

  29. Wang Y, Zhou CH. Recent advances in the researches of triazole compounds as medicinal drugs. Sci Sinca Chim, 2011, 41: 1429–1456 (in Chinese)

    Article  Google Scholar 

  30. Moulin A, Demange L, Ryan J, Mousseaux D, Sanchez P, Bergé G, Gagne D, Perrissoud D, Locatelli V, Torsello A, Galleyrand JC, Fehrentz JA, Martinez J. New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations. J Med Chem, 2008, 51: 689–693

    Article  CAS  Google Scholar 

  31. Fuente RDL, Sonawane ND, Arumainayagam D, Verkman AS. Small molecules with antimicrobial activity against E. coli and P. aeruginosa identified by high-throughput screening. Br J Pharmacol, 2006, 149: 551–559

    Article  Google Scholar 

  32. Kamal A, Adil SF, Tamboli JR, Siddardha B, Murthy USN. Synthesis of coumarin linked naphthalimide conjugates as potential anticancer and antimicrobial agents. Lett Drug Des Discov, 2009, 6: 201–209

    Article  CAS  Google Scholar 

  33. Zhang SL, Damu GLV, Zhang L, Geng RX, Zhou CH. Synthesis and biological evaluation of novel benzimidazole derivatives and their binding behavior with bovine serum albumin. Eur J Med Chem, 2012, 55: 164–175

    Article  CAS  Google Scholar 

  34. Wan K, Zhou CH. Synthesis of novel halobenzyloxy and alkoxy 1,2,4-triazoles and evaluation for their antifungal and antibacterial activities. Bull Korean Chem Soc, 2010, 31: 2003–2010

    Article  CAS  Google Scholar 

  35. Marino JP, Fisher PW, Hofmann GA, Kirkpatrick RB, Janson CA, Johnson RK, Ma C, Mattern M, Meek TD, Ryan MD, Schulz C, Smith WW, Tew DG, Tomazek TA, Veber DF, Xiong WC, Yamamoto Y, Yamashita K, Yang G, Thompson SK. Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore. J Med Chem, 2007, 50: 3777–3785

    Article  CAS  Google Scholar 

  36. Güzeldemirci NU, Küçükbasmacı Ö. Synthesis and antimicrobial activity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b]thiazole moiety. Eur J Med Chem, 2010, 45, 63–68

    Article  Google Scholar 

  37. Ott I, Xu YF, Liu JW, Kokoschka M, Harlos M, Sheldrick WS, Qian XH. Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells. Bioorg Med Chem, 2008, 16: 7107–7116

    Article  CAS  Google Scholar 

  38. Tian ZY, Xie SQ, Mei ZH, Zhao J, Gao WY, Wang CJ. Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway. Org Biomol Chem, 2009, 7: 4651–4560

    Article  CAS  Google Scholar 

  39. Luo Y, Lu YH, Gan LL, Zhou CH, Wu J, Geng RX, Zhang YY. Synthesis, antibacterial and antifungal activities of novel 1,2,4-triazolium derivatives. Arch Pharm, 2009, 342: 386–393

    Article  CAS  Google Scholar 

  40. Ohwada J, Tsukazaki M, Hayase T, Oikawa N, Isshiki Y, Fukuda H, Mizuguchi E, Sakaitani M, Shiratori Y, Yamazaki T, Ichihara S, Umeda I, Shimma N. Design, synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole. Bioorg Med Chem Lett, 2003, 13: 191–196

    Article  CAS  Google Scholar 

  41. Jain AK, Ravichandran V, Sisodiya M, Agrawa RK. Synthesis and antibacterial evaluation of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives. Asian Pac J Trop Med, 2010, 3: 471–474

    Article  CAS  Google Scholar 

  42. Liesen AP, Aquino TM, Carvalho CS, Lima VT, Araújo JM, Lima JG, Faria AR, Melo EJT, Alves AJ, Alves EW, Alves AQ, Góes AJS. Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles. Eur J Med Chem, 2010, 45: 3685–3691

    Article  CAS  Google Scholar 

  43. Özbek N, Katırcıoglu H, Karacan N, Baykal T. Synthesis, characterization and antimicrobial activity of new aliphatic sulfonamide. Bioorg Med Chem, 2007, 15: 5105–5109

    Article  Google Scholar 

  44. Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM, El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur J Med Chem, 2007, 42: 235–242

    Article  CAS  Google Scholar 

  45. Wang QP, Zhang JQ, Damu GLV, Wan K, Zhang HZ, Zhou CH. Synthesis and biological activities of thio-triazole derivatives as new potential antibacterial and antifungal agents. Sci China Chem, 2012, 55: 2134–2153

    Article  CAS  Google Scholar 

  46. Maisetta G, Petruzzelli R, Brancatisano FL, Esin S, Vitali A, Campa M, Batoni G. Antimicrobial activity of human hepcidin 20 and 25 against clinically relevant bacterial strains: Effect of copper and acidic pH. Peptides, 2010, 31: 1995–2002

    Article  CAS  Google Scholar 

  47. Kahle M, Stamm C. Time and pH-dependent sorption of the veterinary antimicrobial sulfathiazole to clay minerals and ferrihydrite. Chemosphere, 2007, 68: 1224–1231

    Article  CAS  Google Scholar 

  48. Huang L, Terakawa M, Zhiyentayev T, Huang YY, Sawayama Y, Jahnke A, Tegos GP, Wharton T, Hamblin MR. Innovative cationic fullerenes as broad-spectrum light-activated antimicrobials. Nanomedicine: NBM, 2010, 6: 442–452

    Article  CAS  Google Scholar 

  49. Zhang FF, Gan LL, Zhou CH. Synthesis, antibacterial and antifungal activities of some carbazole derivatives. Bioorg Med Chem Lett, 2010, 20: 1881–1884

    Article  CAS  Google Scholar 

  50. Fang B, Zhou CH, Rao XC. Synthesis and biological activities of novel amine-derived bis-azoles as potential antibacterial and antifungal agents. Eur J Med Chem, 2010, 45: 4388–4398

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China

    Guri L. V. Damu, QingPeng Wang, HuiZhen Zhang, YiYi Zhang, JingSong Lv & ChengHe Zhou

  2. School of Chemistry and Chemical Engineering, Bijie University, Guizhou, 551700, China

    JingSong Lv

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  1. Guri L. V. Damu
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  2. QingPeng Wang
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  3. HuiZhen Zhang
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  4. YiYi Zhang
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  5. JingSong Lv
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  6. ChengHe Zhou
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Correspondence to JingSong Lv or ChengHe Zhou.

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Postdoctoral fellow from Indian Institute of Chemical Technology (IICT), India

The three authors contributed equally to this work

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Damu, G.L.V., Wang, Q., Zhang, H. et al. A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents. Sci. China Chem. 56, 952–969 (2013). https://doi.org/10.1007/s11426-013-4873-1

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  • DOI: https://doi.org/10.1007/s11426-013-4873-1

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