Screening the antifungal activities of monoterpenes and their isomers against Candida species. - National Genomics Data Center (CNCB-NGDC)

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Screening the antifungal activities of monoterpenes and their isomers against Candida species.

A Iraji, S Yazdanpanah, F Alizadeh, S Mirzamohammadi, Y Ghasemi, K Pakshir, Y Yang, K Zomorodian

Author Information

A Iraji: Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
S Yazdanpanah: Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
F Alizadeh: Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
S Mirzamohammadi: Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Y Ghasemi: Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
K Pakshir: Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Y Yang: Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, China.
K Zomorodian: Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. ORCID

PMID: 32506599 DOI: 10.1111/jam.14740

AIM: Increasing the occurrence of non-albicans Candida species with intrinsic or acquired resistance to antifungals as well as the emergence of multidrug Candida species coupled with the limited antifungal agents challenges the treatment of candidiasis. Consequently, a class of secondary metabolites of plants exhibiting decent antifungal activity. Therefore, this study aimed to evaluate the antifungal potential of various monoterpenes including Carvone, Limonene, Pinene, Menthone, Menthol, Camphor, Thujone, Citronellol, and Piperitone against standard and clinical isolates of Candida.
METHODS AND RESULTS: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of compounds were determined, using the broth Microdilution method based on M27-A3 protocol documented by clinical laboratory standard institute (CLSI). Amongst the tested monoterpenes, oxygenated terpenoids showed strong antifungal activity. Specifically, alcoholic terpenoids such as (±)-Citronellol possess more efficacy than the corresponding ketonic ones with MICs ranging from 0·03 to 2·00 μl ml (0·16-10·80 mmol l ). Among the examined yeasts, Candida tropicalis was the most susceptible species to (±)-Citronellol. Moreover, the examined monoterpenes successfully inhibited the growth of fluconazole-resistant Candida species. Moreover, statistical analysis showed no statistically significant difference between the (+) and (-) isomers, except for (±)-α-Pienene and (±) Menthone (ρ-value < 0·05).
CONCLUSION: Among the tested monoterpenes, (±)-Citronellol was the most potent compounds followed by (+)-α-Pinene and Menthol. Considering the significant antifungal activity of the examined monoterpenes, they could be used in controlling or treating candidiasis. Those potent antifungal monoterpenes with GRAS status in addition to their pleasant taste and odour make them appropriate additive or preservative compounds in food and cosmetics products. Furthermore, these data might help researchers to predict EOs antifungal activities, after determining its constituents.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new information about the antifungal activities of monoterpenes and their isomers presented widely in essential oils. Screening results against pathogenic yeasts confirm the correlation between the chemical structure of tested monoterpenes and their antifungal effects. The present findings might be helpful to anticipate the antifungal activity of essential oils.

Broth microdilution Menthone Yeast minimum inhibitory concentration natural product α-Pienene

Abbaszadegan, A., Sahebi, S., Gholami, A., Delroba, A., Kiani, A., Iraji, A. and Abbott, P.V. (2016) Time-dependent antibacterial effects of Aloe vera and Zataria multiflora plant essential oils compared to calcium hydroxide in teeth infected with Enterococcus faecalis. J Investig Clin Dent 7, 93-101.

Alvarez-Castellanos, P.P., Bishop, C.D. and Pascual-Villalobos, M.J. (2001) Antifungal activity of the essential oil of flowerheads of garland chrysanthemum (Chrysanthemum coronarium) against agricultural pathogens. Phytochemistry 57, 99-102.

Arastehfar, A., Daneshnia, F., Zomorodian, K., Najafzadeh, M.J., Khodavaisy, S., Zarrinfar, H., Hagen, F., Zare Shahrabadi, Z. et al. (2019) Low level of antifungal resistance in Iranian isolates of Candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrob Agents Chemother 63, 2503-2518.

Barreto, R., Albuquerque-Júnior, R., Araújo, A., Almeida, J., Santos, M., Barreto, A., DeSantana, J., Siqueira-Lima, P. et al. (2014) A systematic review of the wound-healing effects of monoterpenes and iridoid derivatives. Molecules 19, 846-862.

Behnam, S., Farzaneh, M., Ahmadzadeh, M. and Tehrani, A.S. (2006) Composition and antifungal activity of essential oils of Mentha piperita and Lavendula angustifolia on post-harvest phytopathogens. Commun Agric Appl Biol Sci 71, 1321-1326.

Ben Arfa, A., Combes, S., Preziosi-Belloy, L., Gontard, N. and Chalier, P. (2006) Antimicrobial activity of carvacrol related to its chemical structure. Lett Appl Microbiol 43, 149-154.

Burt, S. (2004) Essential oils: their antibacterial properties and potential applications in foods-a review. Int J Food Microbiol 94, 223-253.

Cai, R., Hu, M., Zhang, Y., Niu, C., Yue, T., Yuan, Y. and Wang, Z. (2019) Antifungal activity and mechanism of citral, limonene and eugenol against Zygosaccharomyces rouxii. LWT 106, 50-56.

Cakir, A., Kordali, S., Zengin, H., Izumi, S. and Hirata, T. (2004) Composition and antifungal activity of essential oils isolated from Hypericum hyssopifolium and Hypericum heterophyllum. Flavour Fragr J 19, 62-68.

CLSI (2008) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved standard-third edition-document m27-a3. Wayne, PA: CLSI.

Colombo, A.L., Júnior, J.N. and Guinea, J. (2017) Emerging multidrug-resistant Candida species. Curr Opin Infect Dis 30, 528-538.

Cristani, M., D'Arrigo, M., Mandalari, G., Castelli, F., Sarpietro, M.G., Micieli, D., Venuti, V., Bisignano, G. et al. (2007) Interaction of four monoterpenes contained in essential oils with model membranes: implications for their antibacterial activity. J Agric Food Chem 55, 6300-6308.

Dammak, I., Hamdi, Z., Kammoun El Euch, S., Zemni, H., Mliki, A., Hassouna, M. and Lasram, S. (2019) Evaluation of antifungal and anti-ochratoxigenic activities of Salvia officinalis, Lavandula dentata and Laurus nobilis essential oils and a major monoterpene constituent 1,8-cineole against Aspergillus carbonarius. Ind Crops Prod 128, 85-93.

de Castro, R.D., de Souza, T.M.P.A., Bezerra, L.M.D., Ferreira, G.L.S., de Brito Costa, E.M.M. and Cavalcanti, A.L. (2015) Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study. BMC Complement Altern Med 15, 417.

de Oliveira, H.M.B.F., de Oliveira Filho, A.A., de Siqueira Júnior, J.P. and Lima, E.O. (2017) In vitro anti-Candida effect of (S)-(-)-citronellal. J Appl Pharm Sci 7, 177-179.

Dias, I., Trajano, E., Castro, R., Ferreira, G., Medeiros, H. and Gomes, D. (2018) Antifungal activity of linalool in cases of Candida spp. isolated from individuals with oral candidiasis. Braz J Biol 78, 368-374.

Ellis, D.H., Davis, S., Alexiou, H., Handke, R. and Bartley, R. (2007) Descriptions of Medical Fungi. Adelaide: University of Adelaide.

Filipowicz, N., Kamiński, M., Kurlenda, J., Asztemborska, M. and Ochocka, J.R. (2003) Antibacterial and antifungal activity of juniper berry oil and its selected components. Phytother Res 17, 227-231.

Griffin, S., Wyllie, S.G. and Markham, J. (1999a) Determination of octanol-water partition coefficient for terpenoids using reversed-phase high-performance liquid chromatography. J Chromatogr A 864, 221-228.

Griffin, S.G., Wyllie, S.G., Markham, J.L. and Leach, D.N. (1999b) The role of structure and molecular properties of terpenoids in determining their antimicrobial activity. Flavour Frag J 14, 322-332.

Guimarães, A.G., Quintans, J.S. and Quintans-Júnior, L.J. (2013) Monoterpenes with analgesic activity-a systematic review. Phytother Res 27, 1-15.

Jeffery-Smith, A., Taori, S.K., Schelenz, S., Jeffery, K., Johnson, E.M., Borman, A., Manuel, R. and Brown, C.S. (2018) Candida auris: a review of the literature. Clin Microbiol Rev 31, e00029-e17.

Kazemi, M. and Rostami, H. (2015) Chemical composition and biological activities of Iranian Achillea wilhelmsii L. essential oil: a high effectiveness against Candida spp. and Escherichia strains. NAT PROD RES 29, 286-288.

Kazemi, M., Rostami, H. and Shafiei, S. (2012) Antibacterial and antifungal activity of some medicinal plants from Iran. J Plant Sci 7, 55-66.

Khan, A., Ahmad, A., Akhtar, F., Yousuf, S., Xess, I., Khan, L.A. and Manzoor, N. (2010) Ocimum sanctum essential oil and its active principles exert their antifungal activity by disrupting ergosterol biosynthesis and membrane integrity. Res. Microbiol 161, 816-823.

Kontoyiannis, D.P., Vaziri, I., Hanna, H.A., Boktour, M., Thornby, J., Hachem, R., Bodey, G.P. and Raad, I.I. (2001) Risk factors for Candida tropicalis fungemia in patients with cancer. Clin Infect Dis 33, 1676-1681.

Kotan, R., Kordali, S. and Cakir, A. (2007) Screening of antibacterial activities of twenty-one oxygenated monoterpenes. Z Naturforsch C 62, 507-513.

Lamoth, F., Lockhart, S.R., Berkow, E.L. and Calandra, T. (2018) Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother 73, i4-i13.

Ložienė, K., Švedienė, J., Paškevičius, A., Raudonienė, V., Sytar, O. and Kosyan, A. (2018) Influence of plant origin natural α-pinene with different enantiomeric composition on bacteria, yeasts and fungi. Fitoterapia 127, 20-24.

Marei, G.I.K., Abdel Rasoul, M.A. and Abdelgaleil, S.A.M. (2012) Comparative antifungal activities and biochemical effects of monoterpenes on plant pathogenic fungi. Pestic Biochem Phys 103, 56-61.

Martino, L.D., Mancini, E. andAlmeida, L.F.R.D. and Feo, V.D. (2010) The antigerminative activity of twenty-seven monoterpenes. Molecules 15, 6630-6637.

Miceli, M.H., Díaz, J.A. and Lee, S.A. (2011) Emerging opportunistic yeast infections. Lancet Infect Dis 11, 142-151.

Mirhendi, H., Makimura, K., Khoramizadeh, M. and Yamaguchi, H. (2006) A one-enzyme PCR-RFLP assay for identification of six medically important Candida species. Nippon Ishinkin Gakkai Zasshi 47, 225-229.

Mirhendi, H., Makimura, K., Zomorodian, K., Maeda, N., Ohshima, T. and Yamaguchi, H. (2005) Differentiation of Candida albicans and Candida dubliniensis using a single-enzyme PCR-RFLP method. Jpn J Infect Dis 58, 235-237.

Miron, D., Battisti, F., Silva, F.K., Lana, A.D., Pippi, B., Casanova, B., Gnoatto, S., Fuentefria, A. et al. (2014) Antifungal activity and mechanism of action of monoterpenes against dermatophytes and yeasts. Rev Bras Farmacogn 24, 660-667.

Moein, M., Zomorodian, K., Almasi, M., Pakshir, K. and Zarshenas, M.M. (2017) Preparation and analysis of Rosa damascena essential oil composition and antimicrobial activity assessment of related fractions. Iran J Sci Technol A 41, 87-94.

Moran, C., Grussemeyer, C.A., Spalding, J.R., Benjamin, D.K. Jr and Reed, S.D. (2010) Comparison of costs, length of stay, and mortality associated with Candida glabrata and Candida albicans bloodstream infections. Am J Infect Control 38, 78-80.

Passone, M.A., Girardi, N.S. and Etcheverry, M. (2012) Evaluation of the control ability of five essential oils against Aspergillus section Nigri growth and ochratoxin A accumulation in peanut meal extract agar conditioned at different water activities levels. Int J Food Microbiol 159, 198-206.

Pereira Fde, O., Mendes, J.M., Lima, I.O., Mota, K.S., Oliveira, W.A. and Lima Ede, O. (2015) Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharm Biol 53, 228-234.

Pfaller, M. and Diekema, D. (2012) Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol 50, 2846-2856.

Pizzolitto, R., Herrera, J., Zaio, Y., Dambolena, J., Zunino, M., Gallucci, M. and Zygadlo, J. (2015) Bioactivities of ketones terpenes: Antifungal effect on F. verticillioides and repellents to control insect fungal vector, S. zeamais. Microorganisms 3, 851-865.

Rivas da Silva, A.C., Lopes, P.M., Barros de Azevedo, M.M., Costa, D.C., Alviano, C.S. and Alviano, D.S. (2012a) Biological activities of alpha-pinene and beta-pinene enantiomers. Molecules 17, 6305-6316.

Rivas da Silva, A.C., Lopes, P.M., Barros de Azevedo, M.M., Machado Costa, D.C., Alviano, C.S. and Alviano, D.S. (2012b) Biological activities of alpha-pinene and beta-pinene enantiomers. Molecules 17, 6305-6316.

Saharkhiz, M.J., Motamedi, M., Zomorodian, K., Pakshir, K., Miri, R. and Hemyari, K. (2012) Chemical composition, antifungal and antibiofilm activities of the essential oil of Mentha piperita L. ISRN Pharm 2012, 718645.

Samber, N., Khan, A., Varma, A. and Manzoor, N. (2015) Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components. Pharm Biol 53, 1496-1504.

Santos, M.R., Moreira, F.V., Fraga, B.P., Souza, D.P.D., Bonjardim, L.R. and Quintans-Junior, L.J. (2011) Cardiovascular effects of monoterpenes: a review. Rev Bras Farmacogn 21, 764-771.

Shin, S. and Lim, S. (2004) Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp. J Appl Microbiol 97, 1289-1296.

Silva, D.F., Silva, A.C., Diniz-Neto, H., Oliveira, H.M., Medeiros, C.I. and Pereira, J.A. (2018) Activity anti-Candida albicans and Effects of the association of ß-citronellol with three antifungal azolics. Lat Am J Pharm 37, 182-188.

Trombetta, D., Castelli, F., Sarpietro, M.G., Venuti, V., Cristani, M., Daniele, C., Saija, A., Mazzanti, G. et al. (2005) Mechanisms of antibacterial action of three monoterpenes. Antimicrob Agents Chemother 49, 2474-2478.

Turner, S.A. and Butler, G. (2014) The Candida pathogenic species complex. Cold Spring Harb Perspect Med. 4(9), a019778.

Ultee, A., Bennik, M. and Moezelaar, R. (2002) The phenolic hydroxyl group of carvacrol is essential for action against the food-borne pathogen Bacillus cereus. Appl Environ Microbiol 68, 1561-1568.

Xia, Z., Mao, X. and Luo, Y. (1999) Study on antifungal mechanism of alpha-pinene. Bull Hum Medl Uni 24, 507-509.

86-3445/Shiraz University of Medical Sciences
87-4107/Shiraz University of Medical Sciences

Antifungal Agents

Candida

Candidiasis

Drug Resistance, Fungal

Fluconazole

Humans

Microbial Sensitivity Tests

Monoterpenes

Oils, Volatile

Antifungal Agents

Monoterpenes

Oils, Volatile

Fluconazole

Journal Article