Skip to main content
SpringerLink
Log in

Recyclable CuO nanoparticles-catalyzed synthesis of novel-2,5-disubstituted 1,3,4-oxadiazoles as antiproliferative, antibacterial, and antifungal agents

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

Abstract

A series of new 2,5-disubstituted 1,3,4-oxadiazoles have been conveniently synthesized through an oxidative C–O coupling by direct C–H bond activation of N-aroyl-N-arylidinehydrazines using a catalytic quantity of CuO nanoparticles. Twenty compounds have been synthesized in good to excellent yields (75–90 %). All the synthesized compounds were evaluated for their in vitro antiproliferative, antibacterial, and antifungal activity. Compounds 8d and 10d are more promising antiproliferative agents with IC50 value of 3.66 and 3.89 µM in MCF-7 cell line, and compounds 8a and 10a were showed more potent antifungal activity than standard drug.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aboraia AS, Rahman HMA, Mahfouz NM, Gendy MAE (2006) Novel 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: promising anticancer agents. Bioorg Med Chem 14:1236–1246

    Article  CAS  PubMed  Google Scholar 

  • Al-Talib M, Tashtoush H, Odeh N (1990) A convenient synthesis of alkyl and aryl substituted bis-1,3,4-oxadiazoles. Synth Commun 20:1811–1817

    Article  CAS  Google Scholar 

  • Babu SG, Ramasamy K (2011) CuO nanoparticles: a simple, effective, ligand free and reusable heterogeneous catalyst for N-arylation of benzimidazole. Ind Eng Chem Res 50:9594–9600

    Article  Google Scholar 

  • Boström J, Hogner A, Llinàs A, Wellner E, Plowright AT (2012) Oxadiazoles in medicinal chemistry. J Med Chem 55:1817–1830

    Article  PubMed  Google Scholar 

  • Dabiri M, Salehi P, Baghbanzadeh M, Bahramnejad M (2006) A facile procedure for the one-pot synthesis of unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles. Tetrahedron Lett 47:6983–6986

    Article  CAS  Google Scholar 

  • Dogan HN, Duran A, Rollas S, Sener G, Uysal MK, Gulen D (2002) Synthesis of new 2,5-disubstituted-1,3,4-thiadiazoles and preliminary evaluation of anticonvulsant and antimicrobial activities. Bioorg Med Chem 10:2893–2898

    Article  CAS  PubMed  Google Scholar 

  • Flidallah HM, Sharshira EM, Basaif SA, A-Ba-Oum AEK (2002) Phosphorus Sulfur Silicon Relat Elem 177:67–79

  • Guin S, Ghosh T, Rout SK, Banerjee A, Patel BK (2011) Cu(II) catalyzed imine C-H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles. Org Lett 13:5976–5979

    Article  CAS  PubMed  Google Scholar 

  • James ND, Growcott JW (2009) Zibotentan. Drugs Future 34:624–633

    Article  CAS  Google Scholar 

  • Jedlovska E, Lesko J (1994) A simple one-pot procedure for the synthesis of 1,3,4-oxadiazoles. Synth Commun 24:1879–1885

    Article  CAS  Google Scholar 

  • Kantam ML, Soumi L, Yadav J, Suresh B (2008) An efficient synthesis of propargylamines via three-component coupling of aldehydes, amines and alkynes catalyzed by nanocrystalline copper(II) oxide. Tetrahedron Lett 49:3083–3086

    Article  CAS  Google Scholar 

  • Kawano T, Yoshizumi T, Hirano K, Satoh T, Miura M (2009) Copper-mediated direct arylation of 1,3,4-oxadiazoles and 1,2,4-triazoles with aryl iodides. Org Lett 11:3072–3075

    Article  CAS  PubMed  Google Scholar 

  • Kumar GS, Maheswari CU, Kumar RA, Kantam ML, Reddy KR (2011) Copper-catalyzed oxidative C-O coupling by direct C–H bond activation of formamides: synthesis of enol carbamates and 2-carbonyl-substituted phenol carbamates. Angew Chem Int Ed 50:11748–11751

    Article  CAS  Google Scholar 

  • Lee YZ, Chen X, Chen SA, Wei PK, Fann WS (2001) Soluble electroluminescent poly(phenylene vinylene)s with balanced electron- and hole injections. J Am Chem Soc 123:2296–2307

    Article  CAS  PubMed  Google Scholar 

  • Liu K, Lu X, Zhang HJ, Sun J, Zhu HL (2012) Synthesis, molecular modeling, and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as antitumor agents. Eur J Med Chem 47:473–478

    Article  PubMed  Google Scholar 

  • Milcent R, Barbier GJ (1983) Oxydation d’hydrazones par le bioxyde de plomb: Nouvelles synthèses d’oxadiazoles-1,3,4 et de dérivés de l’amino-4 triazol-1,2,4 one-5. Heterocycl Chem 20:77–80

    Article  CAS  Google Scholar 

  • Okimoto M, Chiba T (1990) Electrochemical oxidation of ketone acylhydrazones and their hydrogen cyanide adducts in sodium cyanide-methanol. Transformation of ketones to nitriles. J Org Chem 55:1070–1076

    Article  CAS  Google Scholar 

  • de Oliveira CS, Lira BF, Barbosa-Filho JM, Lorenzo JGF, de Athayde-Filho PF (2012) Synthetic approaches and pharmacological activity of 1,3,4-oxadiazoles: a review of the literature from 2000–2012. Molecules 17:10192–10231

    Article  PubMed  Google Scholar 

  • Ouyang X, Piatnitski EL, Pattaropong V, Chen X, He HY, Kiselyov AS, Velankar A, Kawakami J, Labelle M, Smith L, Lohman J, Lee SP, Malikzay A, Fleming J, Gerlak J, Wang Y, Rosler RL, Zhou K, Mitelman S, Camara M, Surguladze D, Doody JF, Tuma MC (2006) Oxadiazole derivatives as a novel class of antimitotic agents: synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett 16:1191–1196

    Article  CAS  PubMed  Google Scholar 

  • Prakash O, Kumar M, Kumar R, Sharma C, Aneja KR (2010) Hypervalent iodine(III) mediated synthesis of novel unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles as antibacterial and antifungal agents. Eur J Med Chem 45:4252–4257

    Article  CAS  PubMed  Google Scholar 

  • Prakash O, Hussain K, Kumar R, Deepak W, Sharma C, Aneja KR (2011) Synthesis and antimicrobial evaluation of new 1,4-dihydro-4-pyrazolylpyridines and 4-pyrazolylpyridines. Org Med Chem Lett 1:1–5

    Article  PubMed Central  PubMed  Google Scholar 

  • Pushpan P, Boja P, Chandrashekar C, Sunil Kumar B (2012) Design, synthesis and biological evaluation of a novel series of 1,3,4-oxadiazole bearing N-methyl-4-(trifluoromethyl)phenyl pyrazole moiety as cytotoxic agents. Eur J Med Chem 53:203–210

    Article  Google Scholar 

  • Reddy MA, Jain N, Yada D, Kishore C, Vangala JR, Surendra PR, Addlagatta A, Kalivendi SV, Sreedhar B (2011) Design and synthesis of resveratrol-based nitrovinylstilbenes as antimitotic agents. J Med Chem 54:6751–6760

    Article  CAS  PubMed  Google Scholar 

  • Rostamizadeh S, Housaini SAG (2004) Microwave assisted syntheses of 2,5-disubstituted 1,3,4-oxadiazoles. Tetrahedron Lett 45:8753–8756

    Article  CAS  Google Scholar 

  • Rout SK, Guin S, Nath J, Patel BK (2012) An “on-water” exploration of CuO nanoparticle catalysed synthesis of 2-aminobenzothiazoles. Green Chem 14:2491–2498

    Article  CAS  Google Scholar 

  • Saberi D, Heydari A (2013) CuO nanoparticles supported on α-Fe2O3-modified CNTs: a magnetically separable catalyst for oxidative C–O coupling of formamides with 1,3-dicarbonyl compounds. Tetrahedron Lett 54:4178–4180

    Article  CAS  Google Scholar 

  • Shi W, Qian X, Zhang R, Song G (2001) Synthesis and quantitative structure–activity relationships of new 2,5-disubstituted-1,3,4-oxadiazoles. J Agric Food Chem 49:124–130

    Article  CAS  PubMed  Google Scholar 

  • Short FW, Long LM (1969) Synthesis of 5-aryl-2-oxazolepropionic acids and analogs antiinflammatory agents. J Heterocycl Chem 6:707–712

    Article  CAS  Google Scholar 

  • Singh S, Sharma LK, Saraswat A, Siddiqui IR, Kehrib HK, Singh RKP (2013) Electrosynthesis and screening of novel 1,3,4-oxadiazoles as potent and selective antifungal agents. RSC Adv 3:4237–4245

    Article  CAS  Google Scholar 

  • Stokes BJ, Driver TG (2011) Transition metal catalyzed formation of N-Heterocycles via aryl- or vinyl C–H bond amination. Eur J Org Chem 2011:4071–4088

    Article  CAS  Google Scholar 

  • Sugimoto Y, Konoki K, Murata M, Matsushita M, Kanazawa H, Oishi T (2009) Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide. J Med Chem 52:798–806

    Article  CAS  PubMed  Google Scholar 

  • Summa V, Petrocchi A, Bonelli F, Crescenzi B, Donghi M, Ferrara M, Fiore F, Gardelli C, Gonzalez Paz O, Hazuda DJ, Jones P, Kinzel O, Laufer R, Monteagudo E, Muraglia E, Nizi E, Orvieto F, Pace P, Pescatore G, Scarpelli R, Stillmock K, Witmer MV, Rowley M (2008) Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIVAIDS infection. J Med Chem 51:5843–5855

    Article  CAS  PubMed  Google Scholar 

  • Werber G, Bucherri F, Noto R, Gentile M (1977) 1,5-dipolar cycloaddition reactions semicarbazone bromides, 5-alkyl (or aryl)amino-1,3,4-oxadiazole-2-carboxylic acids and their esters. J Heterocycl Chem 14:1385–1388

    Article  CAS  Google Scholar 

  • Zarghi A, Faizi M, Shafaghi B, Ahadian A, Khojastehpoor HR, Zanganeh V, Tabatabaia SA, Shafieec A (2005a) Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists. Bioorg Med Chem Lett 15:3126–3129

    Article  CAS  PubMed  Google Scholar 

  • Zarghi A, Tabatabai SA, Faizi M, Ahadian A, Navabi P, Zanganeh V, Shafiee A (2005b) Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles. Bioorg Med Chem Lett 15:1863–1865

    Article  CAS  PubMed  Google Scholar 

  • Zhang M (2010) Copper catalyzed/mediated aromatic C–H bond functionalization. Appl Organomet Chem 24:269–284

    CAS  Google Scholar 

  • Zhang ZM, Zhang XW, Zhao ZZ, Yan R, Xu R, Gong HB, Zhu HL (2012) Synthesis, biological evaluation and molecular docking studies of 1,3,4-oxadiazole derivatives as potential immunosuppressive agents. Bioorg Med Chem 20:3359–3367

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Wang Y, He Y, Liu L, Zhu Q (2012) Cu-catalyzed oxidative C(sp2)–H cycloetherification of o-arylphenols for the preparation of dibenzofurans. Org Lett 14:1078–1081

    Article  CAS  PubMed  Google Scholar 

  • Zovko A, Gabri MV, Kristina S, Pohleven F, Jakli D, Cimerman NG, Lu Z, Edrada-Ebel RA, Houssen WE, Mancini I, Defant A, Jaspars M, Turk T (2012) Antifungal and antibacterial activity of 3-alkylpyridinium polymeric analogs of marine toxins. Int Biodeterior Biodegrad 68:71–77

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to the Director, Indian Institute of Chemical Technology, Hyderabad for the encouragement, RP thankful to CSIR, New Delhi, India for the award of research fellowships. We thank CSIR for financial support under the 12th Five Year plan projects “Affordable Cancer Therapeutics (ACT)’’ (CSC 0301) and “Small Molecules in Lead Exploration (SMiLE)” (CSC0111).

Author information

Authors and Affiliations

  1. Medicinal Chemistry and Pharmacology Division, Discovery Laboratory, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    M. S. R. Murty & Raju Penthala

  2. Bioengineering and Environmental Center, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    Sudheer Kumar Buddana & R. S. Prakasham

  3. Centre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    Pompi Das, Sowjanya Polepalli & N. Jain

  4. Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    Sreedhar Bojja

Authors
  1. M. S. R. Murty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raju Penthala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sudheer Kumar Buddana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. S. Prakasham
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pompi Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sowjanya Polepalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sreedhar Bojja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. S. R. Murty.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 6063 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murty, M.S.R., Penthala, R., Buddana, S.K. et al. Recyclable CuO nanoparticles-catalyzed synthesis of novel-2,5-disubstituted 1,3,4-oxadiazoles as antiproliferative, antibacterial, and antifungal agents. Med Chem Res 23, 4579–4594 (2014). https://doi.org/10.1007/s00044-014-1025-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1025-x

Keywords

Search

Navigation