Skip to main content

Advertisement

SpringerLink
Log in

Antimicrobial and cytotoxic evaluation of eugenol derivatives

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

Abstract

Eugenol is the major phenolic component of clove essential oil and it has been used in medical and dental practice for its properties like analgesic, local anesthetic, and antioxidant. It is known that eugenol can denature proteins and react with cell membrane phospholipids changing their permeability and inhibiting a great number of Gram-negative and Gram-positive bacteria as well as different types of yeast. Eugenol has ever demonstrated antimicrobial properties; thus, the search for the optimization through structural changes appears to be interesting for the development of new antimicrobials. This study aimed to evaluate the antimicrobial activity and cytotoxic characteristics of eugenol analogs. From natural eugenol, 14 derivatives were obtained by typical acylation and alkylation. Their antimicrobial activity was evaluated by the broth microdilution method. The compounds were assessed against Staphylococcus aureus ATCC 19095, Enterococcus faecalis ATCC 4083, Escherichia coli ATCC29214, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 62342 and the following clinical isolates from the human oral cavity: C. albicans (3), C. parapsilosis C. glabrata C. lipolytica, and C. famata. Cytotoxicity against mouse embryonic fibroblast (NIH/3T3) cell line was evaluated by MTT colorimetric assay. The majority of compounds demonstrated significant antimicrobial activities. In general, the compounds presented very low or no cytotoxicity, with an inhibitory ratio lower than 50 % against NIH/3T3 cell line.

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

Scheme 1
Scheme 2
Fig. 1

Similar content being viewed by others

References

  • Campaniello D, Corbo MR, Sinigaglia M (2010) Antifungal activity of eugenol against penicillium, aspergillus, and fusarium species. J Food Prot 73:1124–1128

    PubMed  Google Scholar 

  • Chaieb K, Hajlaoui H, Zmantar T, et al. (2007) The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phyther Res 21:501–506. doi:10.1002/ptr.2124

    Article  CAS  Google Scholar 

  • Chander MP, Pillai CR, Sunish IP, Vijayachari P (2016) Antimicrobial and antimalarial properties of medicinal plants used by the indigenous tribes of Andaman and Nicobar Islands, India. Microb Pathog 96:85–88. doi:10.1016/j.micpath.2016.04.017

  • CLSI (2008) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard. CLSI Document M27-A3, 3rd edn. Clinical and Laboratory Standards Institute, Wayne, PA

  • Cutler HG, Cutler SJ, Tworkoski T (2002) The synthesis and biological evaluation of eugenol derivatives as potencial herbicidal agents. Plant Growth Regul Soc Am 29:93–98

    Google Scholar 

  • D’Avila Farias M, Oliveira PS, Dutra FSP, et al. (2014) Eugenol derivatives as potential anti-oxidants: Is phenolic hydroxyl necessary to obtain an effect? J Pharm Pharmacol 66:733–746. doi:10.1111/jphp.12197

    Article  PubMed  Google Scholar 

  • Duarte MCT, Figueira GM, Sartoratto A, et al. (2005) Anti-candida activity of Brazilian medicinal plants. J Ethnopharmacol 97:305–311. doi:10.1016/j.jep.2004.11.016

    Article  PubMed  Google Scholar 

  • Fontenelle ROS, Morais SM, Brito EHS, et al. (2011) Alkylphenol activity against Candida spp. and Microsporum canis: A focus on the antifungal activity of thymol, eugenol and o-methyl derivatives. Molecules 16:6422–6431. doi:10.3390/molecules16086422

    Article  CAS  PubMed  Google Scholar 

  • Gill AO, Holley RA (2006) Disruption of Escherichia coli, Listeria monocytogenes and Lactobacillus sakei cellular membranes by plant oil aromatics. Int J Food Microbiol 108:1–9. doi:10.1016/j.ijfoodmicro.2005.10.009

    Article  CAS  PubMed  Google Scholar 

  • Gündoğdu A, Kılıç H, Ulu KA, et al. (2016) [Susceptibilities of multidrug-resistant pathogens responsible for complicated skin and soft tissue infections to standard bacteriophage cocktails].Mikrobiyol Bul 50:215–223

  • Halim NIM, Kassim K, Fadzil AH, Yamin BM (2012) Synthesis, characterisation and antibacterial studies of 1,2–bis(N′-2,3 and 4-methoxybenzoylthioureido)-4-nitrobenzene. APCBEE Procedia 3:129–133. doi:10.1016/j.apcbee.2012.06.058

    Article  CAS  Google Scholar 

  • He M, Du M, Fan M, Bian Z (2007) In vitro activity of eugenol against Candida albicans biofilms. Mycopathologia 163:137–143. doi:10.1007/s11046-007-0097-2

    Article  CAS  PubMed  Google Scholar 

  • Hemalatha R, Nivetha P, Mohanapriya C, et al. (2015) Phytochemical composition, GC-MS analysis, in vitro antioxidant and antibacterial potential of clove flower bud (Eugenia caryophyllus) methanolic extract. J Food Sci Technol 1–10. doi:10.1007/s13197-015-2108-5

  • Henn S, Nedel F, de Carvalho RV, Lund RG, Cenci MS, Pereira-Cenci T, Demarco FF, Piva, E. (2011) Characterization of an antimicrobial dental resin adhesive containing zinc methacrylate. J Mater Sci Mater Med 22:1797–1802. doi:10.1007/s10856-011-4364-x

  • Katz ML, Mueller LV, Polyakov M, Weinstock SF (2006) Where have all the antibiotic patents gone? Nat Biotechnol 24:1529–1531. doi:10.1038/nbt1206-1529

    Article  CAS  PubMed  Google Scholar 

  • Kavanaugh NL, Ribbeck K (2012) Selected antimicrobial essential oils eradicate pseudomonas spp. and Staphylococcus aureus biofilms. Appl Environ Microbiol 78:4057–4061. doi:10.1128/AEM.07499-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • More G, Tshikalange TE, Lall N, et al. (2008) Antimicrobial activity of medicinal plants against oral microorganisms. J Ethnopharmacol 119:473–477. doi:10.1016/j.jep.2008.07.001

    Article  CAS  PubMed  Google Scholar 

  • Nedel F, Begnini K, Carvalho PHDA, et al. (2012) Antiproliferative activity of flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the MCF7, KB, and NIH/3T3 cell lines. J Med Food 15:955–8. doi:10.1089/jmf.2011.0340

    Article  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335. doi:10.1021/np200906s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nuñez L, D’Aquino M (2012) Microbicide activity of clove essential oil (Eugenia Caryophyllata). Brazil J Microbiol 43:1255–1260. doi:10.1590/S1517-83822012000400003

    Article  Google Scholar 

  • Palaniappan K, Holley RA (2010) Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria. Int J Food Microbiol 140:164–168. doi:10.1016/j.ijfoodmicro.2010.04.001

    Article  CAS  PubMed  Google Scholar 

  • Phatthalung PN, Chusri S, Voravuthikunchai SP (2012) Thai ethnomedicinal plants as resistant modifying agents for combating Acinetobacter baumannii infections. BMC Complement Altern Med 12:56, 10.1186/1472-6882-12-56

    Article  PubMed  PubMed Central  Google Scholar 

  • Ritter M, Martins RM, Dias D, Pereira CMP (2014) Recent advances on the synthesis of chalcones with antimicrobial activities: a brief review. 498–508.

  • Ritter M, Martins RM, Rosa SA, et al. (2015) Green synthesis of chalcones and microbiological evaluation. J Brazil Chem Soc 26:1201–1210

    CAS  Google Scholar 

  • Saeed S, Rashid N, Jones PG, et al. (2010) Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. Eur J Med Chem 45:1323–1331. doi:10.1016/j.ejmech.2009.12.016

    Article  CAS  PubMed  Google Scholar 

  • Santana BP, Dos Reis Paganotto GF, Nedel F, et al. (2012) Nano-/microfiber scaffold for tissue engineering: physical and biological properties. J Biomed Mater Res - Part A 100A:3051–3058. doi:10.1002/jbm.a.34242

  • Shad AA, Asmat S, Bakht J, Jan S, Khan MA (2016) Antimicrobial potentials and phytochemical analysis of desert cotton (A. Javanica) and flax (L. Ustitatissimum). Pak J Pharm Sci 29:861–868.

  • Shin S, Pyun MS (2004) Anti-Candida effects of estragole in combination with ketoconazole or amphotericin B. Phyther Res 18:827–830. doi:10.1002/ptr.1573

    Article  CAS  Google Scholar 

  • Stein EM, Colepicolo P, Afonso FAK, Fujii MT (2011) Screening for antifungal activities of extracts of the Brazilian seaweed genus Laurencia (Ceramiales, Rhodophyta). Brazil J Pharmacogn 21:290–295. doi:10.1590/S0102-695X2011005000085

    Google Scholar 

  • Tekwu EM, Pieme AC, Beng VP (2012) Investigations of antimicrobial activity of some Cameroonian medicinal plant extracts against bacteria and yeast with gastrointestinal relevance. J Ethnopharmacol 142:265–273. doi:10.1016/j.jep.2012.05.005

    Article  PubMed  Google Scholar 

  • Thosar N, Basak S, Bahadure RN, Rajurkar M (2013) Antimicrobial efficacy of five essential oils against oral pathogens: an in vitro study. Eur J Dent. doi:10.4103/1305-7456.119078

  • Venkadeswaran K, Thomas PA, Geraldine P (2016) An experimental evaluation of the anti-atherogenic potential of the plant, Piper betle, and its active constitutent, eugenol, in rats fed an atherogenic diet. Biomed Pharmacother 80:276–288. doi:10.1016/j.biopha.2016.03.028

    Article  CAS  PubMed  Google Scholar 

  • Voda K, Boh B, Vrtačnik M (2004) A quantitative structure-antifungal activity relationship study of oxygenated aromatic essential oil compounds using data structuring and PLS regression analysis. J Mol Model 10:76–84. doi:10.1007/s00894-003-0174-5

    Article  CAS  PubMed  Google Scholar 

  • Walsh SE, Maillard JY, Russell AD, et al. (2003) Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria. J Appl Microbiol 94:240–247. doi:10.1046/j.1365-2672.2003.01825.x

    Article  CAS  PubMed  Google Scholar 

  • Zengin G (2011) Synthesis, antimicrobial activity, and structure–activity relationships of eugenol, menthol, and genistein esters. Chem Nat Compd 47:550–555. doi:10.1007/s10600-011-9994-1

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from “Fundação de Amparo à Pesquisa do Rio Grande do Sul” (FAPERGS), “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES) and “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq), Brazil.

Author information

Authors and Affiliations

  1. Technology Development Center, Federal University of Pelotas, Pelotas, RS, Brazil

    Rosiane Mastelari Martins

  2. Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Pelotas, RS, Brazil

    Marília D’Avila Farias, Claudio M. P. de Pereira & Claiton Lencina

  3. School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil

    Fernanda Nedel & Rafael Guerra Lund

Authors
  1. Rosiane Mastelari Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marília D’Avila Farias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernanda Nedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudio M. P. de Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claiton Lencina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rafael Guerra Lund
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rafael Guerra Lund.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martins, R.M., Farias, M.D., Nedel, F. et al. Antimicrobial and cytotoxic evaluation of eugenol derivatives. Med Chem Res 25, 2360–2367 (2016). https://doi.org/10.1007/s00044-016-1682-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-016-1682-z

Keywords

Search

Navigation