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Synthesis and evaluation of novel benzene-ethanol bearing 1,2,4-triazole derivatives as potential antimicrobial agents

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Abstract

The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more efficacious and broad-spectrum antimicrobial agents. In this study, a novel series of triazole derivates that are structurally related to the famous antimicrobial azole pharmacophore were synthesized and the structures of them were characterized by spectral (IR, 1H NMR, 13C NMR, and MS spectra) analysis. Antimicrobial activity was measured against both bacteria and fungus. In vitro antimicrobial evaluation showed that five compounds had growth inhibitory effects on the tested Gram-positive bacteria and fungus with special efficacy. Potential antibacterial and antifungal activities are incorporated in these triazole compounds. Results of antimicrobial activities also revealed that compounds (5a–i) were the potent antibacterial and antifungal agents as compared to standard drugs (ciprofloxacin and itraconazole), and thus could be promising new lead molecules.

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References

  • Abdel-Megeed AM, Abdel-Rahman HM, Alkaramany GS (2009) Design, synthesis and molecular modeling study of acylated 1,2,4-triazole-3-acetates with potential anti-inflammatory activity. Eur J Med Chem 44(1):117–123

    Article  CAS  PubMed  Google Scholar 

  • Akbas E, Berber I (2005) Antibacterial and antifungal activities of new pyrazolo[3,4-d]pyridazin derivatives. Eur J Med Chem 40(4):401–405

    Article  CAS  PubMed  Google Scholar 

  • Al-Qawasmeh RA, Huthail BB, Sinnokrot MO, Semreen MH, Odeh RA, Abu-Zarga MH, Tarazi H, Yousef IA, Al-Tel TH (2016) Design, synthesis and qualitative structure activity relationship evaluations of quinoline-based bisarylimidazoles as antibacterial motifs. Med Chem 12(6):563–573

    Article  CAS  PubMed  Google Scholar 

  • Amir M, Shikha K (2004) Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino) phenyl]acetic acid derivatives. Eur J Med Chem 39(6):535–545

    Article  CAS  PubMed  Google Scholar 

  • Bordie A (2002) Aromatase inhibitors in breast cancer. Trends Endocrinol Metab 13(2):61–65

    Article  Google Scholar 

  • Brueggemeir RW, Hackett JC, Diaz-Cruz ES (2005) Aromatase inhibitors in the treatment of breast cancer. Endocr Rev 26(3):331–345

    Article  Google Scholar 

  • De Vita D, Scipione L, Tortorella S, Mellini P, Di Rienzo B, Simonetti G, D’Auria FD, Panella S, Cirilli R, Di Santo R, Palamara AT (2012) Synthesis and antifungal activity of a new series of 2-(1H-imidazol- 1-y1)-1-phenylethanol derivatives. Eur J Med Chem 49:334–342. doi:10.1016/j.ejmech. 2012.01.034

    Article  PubMed  Google Scholar 

  • Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH (2000) Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms haemophilus influenzae and moraxella catarrhalis. J Med Chem 43(5):953–970. doi:10.1021/jm990373e

    Article  CAS  PubMed  Google Scholar 

  • Grant SM, Clissold SP (1990) Fluconazole A pharmacodynamic and pharmacokinetic properties and therapeutic potential in superficial and systemic mycoses. Drugs 39:877–916

    Article  CAS  PubMed  Google Scholar 

  • Grillot R, Lebeau B (2005) In antimicrobial agents, antibacterials and antifungals. In: Bryskier, A. (ed). ASM press, Washington, DC, pp 1275–1276.

  • Guven OO, Erdogan T, Goker H, Yildiz S (2007) Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers. Bioorg Med Chem Lett 17(8):2233–2236

    Article  PubMed  Google Scholar 

  • Karyotakis NC, Anaissie EJ (1994) The new antifungal azoles: fluconazole and itraconazole. Curr Opin Infect Dis 7(6):658–666

    Article  Google Scholar 

  • Kucukguzel I, Kucukguzel SG, Rollas S, Kiraz M (2001) Some 3-thioxo/alkylthio- 1,2,4- triazoles with a substituted thiourea moiety as possible antimycobacterials. Biorg Med Chem Lett 11(13):1703–1707

    Article  CAS  Google Scholar 

  • Kumar H, Javed SA, Khan SA, Amir M (2008) 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: synthesis and preliminary eva-luation of biological properties. Eur J Med Chem 43(12):2688–2698

    Article  CAS  PubMed  Google Scholar 

  • Lebouvier N, Pagniez F, Duflos M, Pape LP, Na YM, Baut LG, Borgne ML (2007) Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety. Bioorg Med Chem Lett 17(13):3686–3689

    Article  CAS  PubMed  Google Scholar 

  • Marrapu VK, Mittal M, Shivahare R, Gupta S, Bhandari K (2011) Synthesis and evaluation of new furanyl and thiophenyl azoles as antileishmanial agents. Eur J Med Chem 46(5):1694–1700

    Article  CAS  PubMed  Google Scholar 

  • Mathew V, Keshavayya J, Vaidya VP (2006) Heterocyclic system containing bridgehead nitrogen atom:synthesis and pharmacological activities of some substituted 1,2,4-triazolo[3,4-b]-1,3,4 -thiadiazoles. Eur J Med Chem 41(9):1048–1058

    Article  CAS  PubMed  Google Scholar 

  • Metwally KA, Yaseen SH, Lashineel SM, El-Fayomi HM, El-Sadek ME (2007) Non-carboxylic analogues of aryl-propionic acids: synthesis, anti-inflammatory activity and ulcerogenic potential. Eur J Med Chem 42(2):152–160

    Article  CAS  PubMed  Google Scholar 

  • Navidpour L, Shafaroodi H, Abdi K, Amini M, Ghahremani MH, Dehpour AR, Shafiee A (2006) Design, synthesis and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors. Bioorg Med Chem 14(8):2507–2517. doi:10.1016/j.bmc.2005.11.029

    Article  CAS  PubMed  Google Scholar 

  • National Committee for Clinical Laboratory Standards. (2000) Performance standards for antimicrobial susceptibility tests, 7th ed. Approved standard, NCCLS document M2-A7, 20(1) National Committee for Clinical Laboratory Standards, Wayne, PA.

  • Pericherla K, Khedar P, Khungar B, Kumar A (2012) Click chemistry inspired structural modification of azole antifungal agents to synthesize novel ‘drug like’ molecules. Tetrahedron Lett 53(50):6761–6764

    Article  CAS  Google Scholar 

  • Plech T, Kaproń B, Paneth A, Kosikowska U, Malm A, Strzelczyk A, Stączek P, Świątek Ł, Rajtar B, Polz-Dacewicz M (2015) Search for factors affecting antibacterial activity and toxicity of 1,2,4- triazole-ciprofloxacin hybrids. Eur J Med Chem 97:94–103

    Article  CAS  PubMed  Google Scholar 

  • Sheng C, Zhang W, Ji H, Zhang M, Song Y, Xu H, Zhu J, Miao Z, Jiang Q, Yao J, Zhou Y, Zhu J, Lu J (2006) Structure-based optimization of azole antifungal agents by comfa, comsia, and molecular docking. J Med Chem 49(8):2512–2525

    Article  CAS  PubMed  Google Scholar 

  • Sheehan DJ, Hitchcock CA, Sibley CM (1999) Current and emerging azole antifungal agents. Clin Microbiol Rev 12(1):40–79

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun QY, Xu JM, Cao YB, Zhang WN, Wu QY, Zhang DZ (2007) Synthesis of novel triazole derivatives as inhibitors of cytochrome P450 14a-demethylase (CYP51). Eur J Med Chem 42:1226–1233

    Article  CAS  PubMed  Google Scholar 

  • Wahbi Y, Caujolle R, Tournaire C, Payard M, Linas MD, Seguela JP (1995) Aromatic ethers of 1-aryl-2-(1H-azolyl)ethanol: study of antifungal activity. Eur J Med Chem 30(12):955–962

    Article  CAS  Google Scholar 

  • Watkins WJ, Renau TE (2003) In Burger’s medicinal chemistry and drug discovery. Abraham DJ (ed) Chemotherapeutic Agents. 6th edn. vol. 5 John Wiley and Sons, pp 893–896.

  • Wong-Beringer A, Kriengkauykiat J (2003) Systemic antifungal therapy: new options, new challenges. Pharmacotherpay 23(11):1441–1462

    Article  CAS  Google Scholar 

  • Wu Y, Wang D, Gao Y, Feng J, Zhang X (2016) New α-methylene-γ-butyrolactone derivatives as potential fungicidal agents: design, synthesis and antifungal activities. Molecules 21(2):130

    Article  PubMed  Google Scholar 

  • Yin BT, Yan CY, Peng XM, Zhang SL, Rasheed S, Geng RX, Zhou CH (2014) Synthesis and biological evaluation of a-triazolyl chalcones as a new type of potential antimicrobial agents and their interaction with calf thymus DNA and human serum albumin. Eur J Med Chem 71:148–159

    Article  CAS  PubMed  Google Scholar 

  • Zhang HY, Shi DQ (2014) Synthesis and herbicidal activities of 3-trifluoromethyl-5-[3-(trifluoromethyl) phenoxy]-1,2,4-triazol-4-Schiff bases. J Heterocyclic Chem 51(S1):E344–E348

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the fund for the 12th five-year Scientific and Technical Research Plan of Jilin Province Department of Education (No. 2014B002).

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    Authors and Affiliations

    1. School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, People’s Republic of China

      Bochao Li,  Dan Jiang, Shuang Li, Wei Lei, Huiying Wang & Feng Lin

    2. School of Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, People’s Republic of China

      Dawei Zhang & Yumin Zhang

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    1. Bochao Li
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    2. Dawei Zhang
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    3. Yumin Zhang
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    4. Dan Jiang
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    8. Feng Lin
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    Correspondence to Feng Lin.

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    Bochao Li and Dawei Zhang contributed equally to this work

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    Li, B., Zhang, D., Zhang, Y. et al. Synthesis and evaluation of novel benzene-ethanol bearing 1,2,4-triazole derivatives as potential antimicrobial agents. Med Chem Res 26, 44–51 (2017). https://doi.org/10.1007/s00044-016-1724-6

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    • DOI: https://doi.org/10.1007/s00044-016-1724-6

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