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Click chemistry inspired synthesis of piperazine-triazole derivatives and evaluation of their antimicrobial activities

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Abstract

A series of novel piperazine-1,2,3-triazole derivatives, which entailed the bioisosteric replacement of the imidazole moiety and hybridization of two drug scaffolds was prepared by employing the regioselective copper (I)-catalysed azide-alkyne 1,3-dipolar cycloaddition reaction. The synthesized compounds were evaluated for antibacterial activities against Gram-negative (E. Coli and P. Putida), Gram-positive S. Aureus bacteria and fungicidal activities against F. oxysporum, F. gramillarium and F. monalliforme fungi. Compound 7ac′ exhibited moderate but promising antibacterial activity against Gram-negative bacteria and fungicidal activity against F. oxysporum and F. gramillarium.

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References

  • Agalave SG, Maujan SR, Pore VS (2011) Click chemistry: 1,2,3-triazoles as pharmacophores. Chem Asian J 6(10):2696–2718

    Article  CAS  PubMed  Google Scholar 

  • Alvarez R, Velazquez S, San-Felix A, Aquaro S, Clercq ED, Perno C-F, Karlsson A, Balzarini J, Camarasa MJ (1994) 1,2,3-triazole-[2,5-bis-o-(tert-butyldimethylsilyl)-.Beta.-d-ribofuranosyl]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole 2″,2″-dioxide) (tsao) analogs: synthesis and anti-hiv-1 activity. J Med Chem 37(24):4185–4194

    Article  CAS  PubMed  Google Scholar 

  • de Oliveira Assis SP, da Silva MT, de Oliveira RN, de Menezes Lima VL (2012) Synthesis and anti-inflammatory activity of new alkyl-substituted phthalimide 1H-1,2,3-triazole derivatives. Sci World J. doi:10.1100/2012/925925

    Google Scholar 

  • Dömling A, Wang W, Wang K (2012) Chemistry and biology of multicomponent reactions. Chem Rev 112(6):3083–3135

    Article  PubMed Central  PubMed  Google Scholar 

  • Ferreira MLG, Pinheiro LCS, Santos-Filho OA, Peçanha MDS, Sacramento CQ, Machado V, Ferreira VF, Souza TML, Boechat N (2014) Design, synthesis, and antiviral activity of new 1 h-1,2,3-triazole nucleoside ribavirin analogs. Med Chem Res 23(3):1501–1511

    Article  CAS  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

    Article  CAS  PubMed  Google Scholar 

  • Güven ÖÖ, Erdoğan T, Göker H, Yıldız 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 

  • Holub JM, Kirshenbaum K (2010) Tricks with clicks: modification of peptidomimetic oligomers via copper-catalyzed azide-alkyne [3 + 2] cycloaddition. Chem Soc Rev 39(4):1325–1337

    Article  CAS  PubMed  Google Scholar 

  • Horne WS, Yadav MK, Stout CD, Ghadiri MR (2004) Heterocyclic peptide backbone modifications in an α-helical coiled coil. J Am Chem Soc 126(47):15366–15367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hou J, Liu X, Shen J, Zhao G, Wang PG (2012) The impact of click chemistry in medicinal chemistry. Expert Opin Drug Discov 7(6):489–501

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Zhang J, Cao Y, Chai X, Zou Y, Wu Q, Zhang D, Jiang Y, Sun Q (2011) Synthesis, in vitro evaluation and molecular docking studies of new triazole derivatives as antifungal agents. Bioorg Med Chem Lett 21(15):4471–4475

    Article  CAS  PubMed  Google Scholar 

  • Kamal A, Shankaraiah N, Devaiah V, Laxma Reddy K, Juvekar A, Sen S, Kurian N, Zingde S (2008) Synthesis of 1,2,3-triazole-linked pyrrolobenzodiazepine conjugates employing ‘click’ chemistry: DNA-binding affinity and anticancer activity. Bioorg Med Chem Lett 18(4):1468–1473

    Article  CAS  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 

  • Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discov Today 8(24):1128–1137

    Article  CAS  PubMed  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40(11):2004–2021

    Article  CAS  Google Scholar 

  • Manohar S, Khan SI, Rawat DS (2011) Synthesis of 4-aminoquinoline-1,2,3-triazole and 4-aminoquinoline-1,2,3-triazole-1,3,5-triazine hybrids as potential antimalarial agents. Chem Biol Drug Res 78(1):124–136

    Article  CAS  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 

  • 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 

  • Pore VS, Jagtap MA, Agalave SG, Pandey AK, Siddiqi MI, Kumar V, Shukla PK (2012) Synthesis and antifungal activity of 1,5-disubstituted-1,2,3-triazole containing fluconazole analogues. Med Chem Comm 3(4):484–488

    Article  CAS  Google Scholar 

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

    CAS  PubMed Central  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, Lü 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 

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

    Article  CAS  Google Scholar 

  • Wang X-L, Wan K, Zhou C-H (2010) Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities. Eur J Med Chem 45(10):4631–4639

    Article  CAS  PubMed  Google Scholar 

  • Willand N, Desroses M, Toto P, Dirié B, Lens Z, Villeret V, Rucktooa P, Locht C, Baulard A, Deprez B (2010) Exploring drug target flexibility using in situ click chemistry: application to a mycobacterial transcriptional regulator. ACS Chem Biol 5(11):1007–1013

    Article  CAS  PubMed  Google Scholar 

  • Yan S-J, Liu Y-J, Chen Y-L, Liu L, Lin J (2010) An efficient one-pot synthesis of heterocycle-fused 1,2,3-triazole derivatives as anti-cancer agents. Bioorg Med Chem Lett 20(17):5225–5228

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank UGC, New Delhi [Grant No. 39-733/2010 (SR)], for financial support. PK and KP thank UGC, New Delhi, for junior research fellowships.

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Authors and Affiliations

  1. Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031, Rajasthan, India

    Poonam Khedar, Kasiviswanadharaju Pericherla & Anil Kumar

  2. Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, 333031, Rajasthan, India

    Rajnish Prakash Singh & Prabhat Nath Jha

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  1. Poonam Khedar
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  2. Kasiviswanadharaju Pericherla
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  3. Rajnish Prakash Singh
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  4. Prabhat Nath Jha
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  5. Anil Kumar
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Correspondence to Anil Kumar.

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Khedar, P., Pericherla, K., Singh, R.P. et al. Click chemistry inspired synthesis of piperazine-triazole derivatives and evaluation of their antimicrobial activities. Med Chem Res 24, 3117–3126 (2015). https://doi.org/10.1007/s00044-015-1361-5

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  • DOI: https://doi.org/10.1007/s00044-015-1361-5

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