Skip to main content

Advertisement

Log in

Synthesis of some novel purine derivatives incorporating tetrazole ring and investigation of their antimicrobial activity and DNA interactions

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

This work describes a novel purine derivatives incorporating tetrazole ring for biological applications. Initially, (6-aminopurin-9-yl)alkanenitrile compounds were synthesized. Then, 9-((1H-tetrazol-5-yl)alkyl)-9H-purin-6-amine compounds were synthesized via the addition of sodium azide to nitrile group. These novel purine analogues incorporating tetrazole ring were characterized by Fourier transform infrared, nuclear magnetic resonance and mass spectroscopic techniques. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains. The effect of the compounds on pBR322 plasmid DNA was studied by gel electrophoretic mobility measurements. The antibacterial activities and plasmid DNA interaction studies suggest that purine derivatives incorporating tetrazole ring cause DNA damages, and higher antibacterial activities than other derivatives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Scheme 2
Fig. 1

Similar content being viewed by others

References

  • Ashour FA, Rida SM, El-Hawash SAM, ElSemary MM, Badr MH (2012) Synthesis, anticancer, anti-HIV-1, and antimicrobial activity of some tricyclic triazino and triazolo [4, 3-e] purine derivatives. Med Chem Res 21:1107–1119

    Article  CAS  Google Scholar 

  • Beena, Rawat DS (2013) Antituberculosis drug research: a critical overview. Med Res Rev 33:693–764

    Article  CAS  PubMed  Google Scholar 

  • Bonan CD, Amaral OB, Rockenbach IC, Walz R, Battastini AMO, Izquierdo I, Sarkis JJF (2000) Altered ATP hydrolysis induced by pentylenetetrazol kindling in rat brain synaptosomes. Neurochem Res 25:775–779

    Article  CAS  PubMed  Google Scholar 

  • Dilek-Celik G, Dişli A, Öner Y, Açık L (2012) Synthesis of some novel thiocyanotopurine derivatives and investigation of their antimicrobial activity and DNA interactions. Chem Pharm Bull 60:578–582

    PubMed  Google Scholar 

  • Dilek-Celik G, Dişli A, Öner Y, Açık L (2013) Synthesis of some novel amino and thiotetrazole purine derivatives and investigation of their antimicrobial activity and DNA interactions. Med Chem Res 22:1470–1479

    Article  CAS  Google Scholar 

  • Erkhtueva EB, Dogadina AV, Khramchikhin AV, Ionin BI (2013) Reaction of chloroacetylenephosphonates with 5-thiotetrazoles. Tetrahedron Lett 54:5174–5177

    Article  Google Scholar 

  • Frija LMT, Ismael A, Cristiano MLS (2010) Photochemical transformations of tetrazole derivatives: applications in organic synthesis. Molecules 15:3757–3774

    Article  CAS  PubMed  Google Scholar 

  • Galmarini CM, Mackey JR, Dumontet C (2002) Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol 3:415–424

    Article  CAS  PubMed  Google Scholar 

  • Hakimelahi GH, Ly TW, Moosavi-Movahedi AA, Jain ML, Zakerinia M, Davari H, Mei HC, Sambaiah T, Moshfegh AA, Hakimelahi S (2001) Design, synthesis, and biological evaluation of novel nucleoside and nucleotide analogues as agents against DNA viruses and/or retroviruses. J Med Chem 44:3710–3720

    Article  CAS  PubMed  Google Scholar 

  • Hirokawa Y, Kinoshita H, Tanaka T, Nakamura T, Fujimoto K, Kashimoto S, Kojima T, Kato S (2009) Pleuromutin derivatives having a purine ring. Part 2: influence of the central spacer on the antibacterial activity against gram-positive pathogens. Bioorg Med Chem Lett 19:170–174

    Article  CAS  PubMed  Google Scholar 

  • Hockova D, Budesinsky M, Marek R, Marek J, Holy A (1999) Regioselective preparation of N7- and N9-alkyl derivatives of N6-[(dimethylamino)methylene] adenine bearing an active methylene group and their further derivatization leading to α-branched acyclic nucleoside analogues. Eur J Org Chem 1999:2675–2682

    Article  Google Scholar 

  • Jacobson KA, Balasubramanian R, Deflorian F, Gao Z-G (2012) G-protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal 8:419–436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lambert JS, Seidlin M, Reichman RC, Plank CS, Laverty M, Morse GD, Knupp C, McLaren C, Pettinelli C, Valentine FT, Dolin R (1990) 2′,3′-Dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex: a phase I trial. N Engl J Med 19:1333–1340

    Article  Google Scholar 

  • Leonard NJ, Lambert RF (1969) Synthetic spectroscopic models realted to coenzymes and base pairs. VI. Synthesis of (.omega.-aralkyl)-6,7-dimethylisoalloxazines, spectroscopic model compounds related to FAD. J Org Chem 34:3240–3248

    Article  CAS  Google Scholar 

  • Mishra AK, Verma S (2010) Interconnected trimeric, pentameric, and hexameric metallacycles in a singular silver–adenine framework. Inorg Chem 49:8012–8016

    Article  CAS  PubMed  Google Scholar 

  • Myznikov LV, Koldobskii GI (2007) Drugs in the tetrazole series. Chem Heterocycl Compd 43:1–9

    Article  CAS  Google Scholar 

  • Özkan H, Yavuz S, Dişli A, Yıldırır Y, Türker L (2007) Synthesis of novel 5-aryl-1H-tetrazoles. Heteroat Chem 18(3):255–258

    Article  Google Scholar 

  • Park AY, Kim WH, Kang JA, Lee HJ, Lee CK, Moon HR (2011) Synthesis of enantiomerically pure d- and l-bicyclo[3.1.0]hexenyl carbanucleosides and their antiviral evaluation. Bioorg Med Chem 19:3945–3955

    Article  CAS  PubMed  Google Scholar 

  • Patil UB, Kumthekar KR, Nagarkar JM (2012) A novel method for the synthesis of 5-substituted 1H-tetrazole from oxime and sodium azide. Tetrahedron Lett 53:3706–3709

    Article  CAS  Google Scholar 

  • Pini E, Rossi E, Ferraris PC, Stradi R (2000) Synthesis of purine derivatives of potential immunomodulatory activity. Boll Chim Farm 139:107–113

    CAS  PubMed  Google Scholar 

  • Proszenyak A, Charnock C, Hedner E, Larsson R, Bohlin L, Gundersen LL (2007) Synthesis, antimicrobial and antineoplastic activities for agelasine and agelasimine analogs with a β-cyclocitral derived substituent. Arch Pharm Chem Life Sci 340:625–634

    Article  CAS  Google Scholar 

  • Qu GR, Zhao L, Wang DC, Wu J, Guo HM (2008) Microwave-promoted efficient synthesis of C6-cyclo secondary amine substituted purine analogues in neat water. Green Chem 10:287–289

    Article  CAS  Google Scholar 

  • Santhoshi A, Sadhu PS, Sriram R, Kumar CNSSP, Mahendar B, Sarangapani M, Rao VJ (2013) A facile route for the synthesis 1,4-disubstituted tetrazolone derivatives and evaluation of their antimicrobial activity. Med Chem Res 22:3329–3340

    Article  CAS  Google Scholar 

  • Shanmugam G, Elavarasan S, Bhakiaraj, Gopalakrishnan M (2013) Simple and efficient method for the preparation of novel tetrazole derivatives spectral characterization and its antibacterial activities. Der Pharma Chemica 5:183–188

    CAS  Google Scholar 

  • Shelkar R, Singh A, Negarkar J (2013) Amberlyst-15 catalyzed synthesis of 5-substituted 1-H-tetrazole via [3 + 2] cycloaddition of nitriles and sodium azide. Tetrahedron Lett 54:106–109

    Article  CAS  Google Scholar 

  • Song WH, Liu MM, Zhong DW, Zhu YL, Bosscher M, Zhou L, Ye DY, Yuan ZH (2013) Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents. Bioorg Med Chem Lett 23:4528–4531

    Article  CAS  PubMed  Google Scholar 

  • Tunçbilek M, Ateş-Alagöz, Zeynep, Altanlar N, Karayel A, Özbey S (2009) Synthesis and antimicrobial evaluation of some new substituted purine derivatives. Bioorg Med Chem 17:1693–1700

    Article  PubMed  Google Scholar 

  • Varadaraji D, Suban SS, Ramasamy VR, Kubendiran K, Raguraman JSKG, Nalilu SK, Pati HN (2010) Synthesis and evaluation of a series of 1-substituted tetrazole derivatives as antimicrobial agents. Org Commun 3:45–56

    CAS  Google Scholar 

  • Yavuz S, Aydın Ö, Çete S, Dişli A, Yıldırır Y (2010) Synthesis and antimicrobial activity studies of some novel substituted phenylhydrazono-1H-tetrazol-5-ylacetonitriles. Med Chem Res 19:120–126

    Article  CAS  Google Scholar 

  • Yıldırır Y, Us MF, Çolak N, Özkan H, Yavuz S, Disli A, Ozturk S, Turker L (2009) The synthesis and investigation of the antimicrobial activity of some new phenylselanyl-1-(toluene-4-sulfonyl)-1H-tetrazole derivatives. Med Chem Res 18:91–97

    Article  Google Scholar 

  • Zhang L, Fan J, Vu K, Hong K, Brazidec J-YL, Shi J, Biamonte M, Busch DJ, Lough RE, Grecko R, Ran Y, Sensintaffar JL, Kamal A, Lundgren K, Burrows FJ, Mansfield R, Timony GA, Ulm EH, Kasibhatla SR, Boehm MF (2006) 7’-substituted benzothiazolothio- and pyridinothiazolothio-purines as potent heat shock protein 90 inhibitors. J Med Chem 49:5352–5362

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work is supported by Gazi University Scientific Research Projects Unit (Project # 05/2011-15). S. Kinali-Demirci acknowledges TUBITAK (Project # 112T868) for the national PhD study scholarship.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Selin Kinali-Demirci or Ali Dişli.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kinali-Demirci, S., İdil, Ö. & Dişli, A. Synthesis of some novel purine derivatives incorporating tetrazole ring and investigation of their antimicrobial activity and DNA interactions. Med Chem Res 24, 1218–1225 (2015). https://doi.org/10.1007/s00044-014-1209-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1209-4

Keywords

Navigation