We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Eugenol and derivatives activity against Mycobacterium tuberculosis, nontuberculous mycobacteria and other bacteria

    Aryadne L de Almeida

    *Author for correspondence:

    E-mail Address: aryadnelalmeida@gmail.com

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    ,
    Katiany R Caleffi-Ferracioli

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    ,
    Regiane B de L Scodro

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    ,
    Vanessa P Baldin

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    ,
    Débora C Montaholi

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    ,
    Luiza F Spricigo

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    ,
    Sandra S Nakamura-Vasconcelos

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    ,
    Laíse A Hegeto

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    ,
    Eloísa G Sampiron

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    ,
    Giovana F Costacurta

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    ,
    Diego A dos S Yamazaki

    Department of Chemistry, State University of Maringa, Parana, Brazil

    ,
    Gisele de F Gauze

    Department of Chemistry, State University of Maringa, Parana, Brazil

    ,
    Vera LD Siqueira

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    &
    Rosilene F Cardoso

    **Author for correspondence:

    E-mail Address: rfcardoso@uem.br

    Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil

    Postgraduate Program in Health Sciences, Health Sciences Center, State University of Maringa, PR, Brazil

    Published Online:https://doi.org/10.2217/fmb-2018-0333

    Aim: To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. Materials & methods: Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter. The cytotoxicity was carried out in macrophages, HeLa and VERO cells. Results: EUG and derivatives displayed activity and synergic effect of EUG combined with rifampicin, isoniazid, ethambutol, and pyrazinamide in Mtb including multidrug-resistant isolates, with more selectivity to bacillus than macrophages, HeLa and VERO cells (selective index from 0.65 to 31.4). EUG derivatives (4-allyl-2-methoxyphenyl acetate, 4-allyl-2-methoxyphenyl benzoate, and 4-allyl-2-methoxyphenyl 4-nitrobenzoate) were more active against nontuberculous mycobacteria than EUG. EUG and derivatives exhibited low activity in other Gram-positive and -negative bacteria. Conclusion: EUG and its derivatives show activity against Mycobacterium spp. and synergic effect of EUG combined with antituberculosis drugs against Mtb.

    Papers of special note have been highlighted as: • of interest

    References

    • 1 WHO. Global Tuberculosis Report 2017. http://apps.who.int/iris/bitstream/10665/259366/1/9789241565516-eng.pdf?ua=1.
    • 2 Covert TC, Rodgers MR, Reyes AL et al. Occurrence of nontuberculous mycobacteria in environmental samples. Appl. Environ. Microbiol. 65(6), 2492–2496 (1999).
    • 3 Johnson MM, Odell JA. Nontuberculous mycobacterial pulmonary infections. J. Thorac. Dis. 6(3), 210–220 (2014).
    • 4 Maitre T, Aubry A, Jarlier V et al. Tuberculoses à bacilles multi- et ultrarésistants. Med. Mal. Infect. 47(1), 3–10 (2017).
    • 5 Dorman HJ, Deans SG. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J. Appl. Microbiol. 88(2), 308–316 (2000).
    • 6 Ahmad A, Wani MY, Khan A et al. Synergistic interactions of eugenol-Tosylate and its congeners with fluconazole against Candida albicans. PLoS ONE 10(12), 1–19 (2015).
    • 7 Ulrich-Merzenich GS. Combination screening of synthetic drugs and plant derived natural products-Potential and challenges for drug development. Synergy 1(1), 59–69 (2014).
    • 8 Nejad SM. Evaluation of cytotoxicity and genotoxicity of eugenol in lymphocytes (2014). www.openaccess.hacettepe.edu.tr:8080/xmlui/bitstream/handle/11655/1142/dd98dce8-0d90-4e43-b495-5e5975b9399d.pdf?sequence=1.
    • 9 Pinto E, Vale-Silva L, Cavaleiro C et al. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. J. Med. Microbiol. 58(11), 1454–1462 (2009).
    • 10 Leite AM, Lima EDO, De Souza EL et al. Inhibitory effect of β -pinene, α -pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria. Brazilian J. Pharm. Sci. 43(1), 121–126 (2007). • Evaluates the activity of eugenol against pathogenic bacteria that cause endocarditis.
    • 11 Yadav MK, Chae S, Im GJ et al. Eugenol: a phyto-compound effective against methicillin-resistant and methicillin- sensitive Staphylococcus aureus clinical strain biofilms. PLoS ONE 10(3), 1–21 (2015). • Demonstrates that eugenol exhibits notable activity against MRSA and MSSA clinical strains biofilms.
    • 12 Devi KP, Nisha SA, Sakthivel R et al. Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. J. Ethnopharmacol. 130(1), 107–115 (2010). • Evaluates the antibacterial activity of eugenol and its mechanism of bactericidal action against Salmonella typhi.
    • 13 Gill AO, Holley RA. Mechanisms of bactericidal action of cinnamaldehyde against Listeria monocytogenes and of. Appl. Environ. Microbiol. 70(10), 5750–5755 (2004).
    • 14 Yogalakshmi B, Viswanathan P, Anuradha CV. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology 268(3), 204–212 (2010).
    • 15 Palomino J, Martin A, Camacho M et al. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrobail Agents Chemother. 46(8), 2720–2722 (2002).
    • 16 CLSI. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes; approved standard (2nd Edition). https://clsi.org/media/1463/m24a2_sample.pdf.
    • 17 Castilho AL, Caleffi-Ferracioli KR, Canezin PH et al. Detection of drug susceptibility in rapidly growing mycobacteria by resazurin broth microdilution assay. J. Microbiol. Methods 111, 119–121 (2015).
    • 18 Caleffi-Ferracioli KR, Maltempe FG, Siqueira VLD et al. Fast detection of drug interaction in Mycobacterium tuberculosis by a checkerboard resazurin method. Tuberculosis 93(6), 660–663 (2013).
    • 19 Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 52(1), 1–1 (2003).
    • 20 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63 (1983).
    • 21 Protopopova M, Hanrahan C, Nikonenko B et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1, 2-ethylenediamines. J. Antimicrob. Chemother. 56(5), 968–974 (2005).
    • 22 Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 1–13 (2017).
    • 23 Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 1(4), 337–341 (2004).
    • 24 Nakamura de Vasconcelos SS, Caleffi-Ferracioli KR, Hegeto LA et al. Carvacrol activity & morphological changes in Mycobacterium tuberculosis. Future Microbiol. 13(8), 877–888 (2018). • This study was the reference for the chemical derivation proposal performed in the present study.
    • 25 Bar FMA, Khanfar MA, Elnagar AY et al. Bioorganic & medicinal chemistry design and pharmacophore modeling of biaryl methyl eugenol analogs as breast cancer invasion inhibitors. Bioorg. Med. Chem. 18(2), 496–507 (2010).
    • 26 Oyedemi SO, Okoh AI, Mabinya LV et al. The proposed mechanism of bactericidal action of eugenol, -terpineol and γ -terpinene against Listeria. African J. Biotechnol. 8(7), 1280–1286 (2009).
    • 27 Coll P. Fármacos con actividad frente a Mycobacterium tuberculosis. Enferm. Infecc. Microbiol. Clin. 27(8), 474–480 (2009).
    • 28 Qiu J, Feng H, Lu J et al. Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus. Appl. Environ. Microbiol. 76(17), 5846–5851 (2010).
    • 29 Mohammed MJ, Al-Bayati FA. Isolation and identification of antibacterial compounds from Thymus kotschyanus aerial parts and Dianthus caryophyllus flower buds. Phytomedicine 16(6–7), 632–637 (2009).
    • 30 Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: clinicians’ perspectives. Tuberc. Respir. Dis. (Seoul). 79(2), 74–84 (2016).
    • 31 Chraibi M, Farah A, Lebrazi S et al. Antimycobacterial natural products from Moroccan medicinal plants: chemical composition, bacteriostatic and bactericidal profile of Thymus satureioides and Mentha pulegium essential oils. Asian Pac. J. Trop. Biomed. 6(10), 836–840 (2016).
    • 32 Peruč D, Gobin I, Abram M et al. Antimycobacterial potential of the juniper berry essential oil in tap water. Arh. Hig. Rada Toksikol. 69(1), 46–54 (2018).
    • 33 Zanetti S, Cannas S, Molicotti P et al. Evaluation of the antimicrobial properties of the essential oil of Myrtus communis L. against clinical strains of Mycobacterium spp. Interdiscip. Perspect. Infect. Dis. 2010, 1–3 (2010).
    • 34 Bueno J, Escobar P, Martinez JR et al. Composition of three essential oils, and their mammalian cell toxicity and antimycobacterial activity against drug resistant-tuberculosis and nontuberculous mycobacteria strains. Nat. Prod. Commun. 6(11), 1743–1748 (2011).
    • 35 Jarlier V, Nikaido H. Permeability barrier to hydrophilic solutes in Mycobacterium chelonei. J. Bacteriol. 172(3), 1418–1423 (1990).
    • 36 Rutkowska E, Pajak K, Jóźwiak K. Lipophilicity - Methods of determination and its role in medicinal chemistry. Acta Pol. Pharm. - Drug Res. 70(1), 3–18 (2013).
    • 37 Sieniawska E, Sawicki R, Swatko-ossor M et al. The effect of combining natural terpenes and antituberculous agents against reference and clinical Mycobacterium tuberculosis strains. Molecules 23(176), 1–14 (2018).
    • 38 Ehab AA, Galal AM, Shebl AM et al. Enhancing effect of isoeugenol on the antimicrobial activity of isoniazid, 6-paradol and 6-shogaol. J. Herbs. Spices Med. Plants 13(4), 95–103 (2008).
    • 39 Hegeto LA, Caleffi-Ferracioli KR, Nakamura-Vasconcelos SS et al. In vitro combinatory activity of piperine and anti-tuberculosis drugs in Mycobacterium tuberculosis. Tuberculosis 111, 35–40 (2018).
    • 40 Barros Gomes PR, Mouchrek Filho VE, Ferreira Rabêlo W et al. Caracterização química e citotoxicidade do óleo essencial do cravo-da-índia (Syzygium aromaticum). Rev. Colomb. Ciencias Químico-Farmacéuticas. 47(1), 37–52 (2018).