Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes
Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on...
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| Veröffentlicht in: | Letters in applied microbiology 2021-03, Vol.72 (3), p.292-298 |
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| creator | Pinto, Â.V. Oliveira, J.C. Costa de Medeiros, C.A. Silva, S.L. Pereira, F.O. |
| description | Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on mechanisms that confer multiple drug resistance. This study investigated the modulating activity of terbinafine promoted by dihydrojasmone and terpinolene against Microsporum canis LM 216, Trichophyton interdigitale H6 and T. interdigitale Δmdr2. The minimum inhibitory concentration (MIC) of test drugs was determined by broth microdilution. The effect of the drugs tested on plasma membrane functionality was analysed. Terbinafine MIC was determined in sub‐inhibitory concentrations of monoterpenes. Finally, it was performed an association study with terbinafine and monoterpenes. Dihydrojasmone presented lower MIC values than terpinolene. All fungi were sensitive to terbinafine, starting at 1 μg ml−1. All tested drugs increased K+ release (P |
| doi_str_mv | 10.1111/lam.13371 |
| format | Article |
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Significance and Impact of the Study: This is the first study that describes the dihydrojasmone and terpinolene action enhancing the antifungal activity of terbinafine against dermatophytes. In vitro tests have demonstrated that the monoterpenes act on the plasma membrane, positively modulating the sensitivity of fungal strains to terbinafine by a synergism association. We suggest that monoterpenes can be an effective and sustainable alternative while contributing to the reduction of the dermatophytes resistance to conventional drugs.</description><identifier>ISSN: 0266-8254</identifier><identifier>EISSN: 1472-765X</identifier><identifier>DOI: 10.1111/lam.13371</identifier><identifier>PMID: 32790923</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antifungal activity ; Antifungal agents ; Antifungal Agents - pharmacology ; Arthrodermataceae - drug effects ; Cyclohexane Monoterpenes - pharmacology ; Dermatomycoses - drug therapy ; Dermatomycosis ; Dermatophytoses ; Drug delivery ; Drug resistance ; Drugs ; Etiology ; Fungi ; Fungicides ; Humans ; in vitrostudies ; Membranes ; Microbial Sensitivity Tests ; Microsporum - drug effects ; Minimum inhibitory concentration ; Monoterpenes ; Monoterpenes - pharmacology ; Multidrug resistance ; Sensitivity ; Synergism ; Terbinafine ; Terbinafine - pharmacology ; Terpinolene</subject><ispartof>Letters in applied microbiology, 2021-03, Vol.72 (3), p.292-298</ispartof><rights>2020 The Society for Applied Microbiology</rights><rights>2020 The Society for Applied Microbiology.</rights><rights>Copyright © 2021 The Society for Applied Microbiology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-741c828e017f500f5dfecf714b9794b46815d4ace2b742836b449d13cc90e5733</citedby><cites>FETCH-LOGICAL-c3531-741c828e017f500f5dfecf714b9794b46815d4ace2b742836b449d13cc90e5733</cites><orcidid>0000-0002-3081-4174 ; 0000-0001-7168-7725 ; 0000-0001-8426-2726 ; 0000-0003-3240-8767 ; 0000-0002-1257-2749</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Flam.13371$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Flam.13371$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32790923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pinto, Â.V.</creatorcontrib><creatorcontrib>Oliveira, J.C.</creatorcontrib><creatorcontrib>Costa de Medeiros, C.A.</creatorcontrib><creatorcontrib>Silva, S.L.</creatorcontrib><creatorcontrib>Pereira, F.O.</creatorcontrib><title>Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes</title><title>Letters in applied microbiology</title><addtitle>Lett Appl Microbiol</addtitle><description>Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on mechanisms that confer multiple drug resistance. This study investigated the modulating activity of terbinafine promoted by dihydrojasmone and terpinolene against Microsporum canis LM 216, Trichophyton interdigitale H6 and T. interdigitale Δmdr2. The minimum inhibitory concentration (MIC) of test drugs was determined by broth microdilution. The effect of the drugs tested on plasma membrane functionality was analysed. Terbinafine MIC was determined in sub‐inhibitory concentrations of monoterpenes. Finally, it was performed an association study with terbinafine and monoterpenes. Dihydrojasmone presented lower MIC values than terpinolene. All fungi were sensitive to terbinafine, starting at 1 μg ml−1. All tested drugs increased K+ release (P < 0·05), affecting the functionality of the plasma membrane. Dihydrojasmone modulated the sensitivity of all strains against terbinafine, and terpinolene modulated the sensitivity of M. canis LM 216 and T. interdigitale Δmdr2. The monoterpenes and terbinafine drug associations presented synergism. In conclusion, the results suggest that the dihydrojasmone and terpinolene are promising antifungal agents that potentiate the antifungal activity of terbinafine against dermatophytes.
Significance and Impact of the Study: This is the first study that describes the dihydrojasmone and terpinolene action enhancing the antifungal activity of terbinafine against dermatophytes. In vitro tests have demonstrated that the monoterpenes act on the plasma membrane, positively modulating the sensitivity of fungal strains to terbinafine by a synergism association. We suggest that monoterpenes can be an effective and sustainable alternative while contributing to the reduction of the dermatophytes resistance to conventional drugs.</description><subject>Antifungal activity</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - pharmacology</subject><subject>Arthrodermataceae - drug effects</subject><subject>Cyclohexane Monoterpenes - pharmacology</subject><subject>Dermatomycoses - drug therapy</subject><subject>Dermatomycosis</subject><subject>Dermatophytoses</subject><subject>Drug delivery</subject><subject>Drug resistance</subject><subject>Drugs</subject><subject>Etiology</subject><subject>Fungi</subject><subject>Fungicides</subject><subject>Humans</subject><subject>in vitrostudies</subject><subject>Membranes</subject><subject>Microbial Sensitivity Tests</subject><subject>Microsporum - drug effects</subject><subject>Minimum inhibitory concentration</subject><subject>Monoterpenes</subject><subject>Monoterpenes - pharmacology</subject><subject>Multidrug resistance</subject><subject>Sensitivity</subject><subject>Synergism</subject><subject>Terbinafine</subject><subject>Terbinafine - pharmacology</subject><subject>Terpinolene</subject><issn>0266-8254</issn><issn>1472-765X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10U9L5DAYBvAgijPOetgvIAUv66FO_rVpjyKrLozowQVvJU3fOBnaZExSl357M467hwVzCe_Lj4eQB6HvBF-SdJa9HC4JY4IcoDnhguaiLJ4P0RzTsswrWvAZOglhgzGuCK2P0YxRUeOasjnaPLoINhoZjbOZ05lMgx7ti-wzqaJ5M3HarSP41lipjYWsnbLOrKfOu40Mg0sbabud2BrretjNL9LYELMO_CCj266nCOEbOtKyD3D6eS_Q75ufT9d3-erh9tf11SpXrGAkF5yoilaAidAFxrroNCgtCG9rUfOWlxUpOi4V0FZwWrGy5bzuCFOqxlAIxhboxz53693rCCE2gwkK-l5acGNoKGecC85wlej5f3TjRm_T65KqKaUcizKpi71S3oXgQTdbbwbpp4bgZldAkwpoPgpI9uwzcWwH6P7Jvz-ewHIP_pgepq-TmtXV_T7yHRHxkFI</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Pinto, Â.V.</creator><creator>Oliveira, J.C.</creator><creator>Costa de Medeiros, C.A.</creator><creator>Silva, S.L.</creator><creator>Pereira, F.O.</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7ST</scope><scope>7T7</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3081-4174</orcidid><orcidid>https://orcid.org/0000-0001-7168-7725</orcidid><orcidid>https://orcid.org/0000-0001-8426-2726</orcidid><orcidid>https://orcid.org/0000-0003-3240-8767</orcidid><orcidid>https://orcid.org/0000-0002-1257-2749</orcidid></search><sort><creationdate>202103</creationdate><title>Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes</title><author>Pinto, Â.V. ; Oliveira, J.C. ; Costa de Medeiros, C.A. ; Silva, S.L. ; Pereira, F.O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-741c828e017f500f5dfecf714b9794b46815d4ace2b742836b449d13cc90e5733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antifungal activity</topic><topic>Antifungal agents</topic><topic>Antifungal Agents - pharmacology</topic><topic>Arthrodermataceae - drug effects</topic><topic>Cyclohexane Monoterpenes - pharmacology</topic><topic>Dermatomycoses - drug therapy</topic><topic>Dermatomycosis</topic><topic>Dermatophytoses</topic><topic>Drug delivery</topic><topic>Drug resistance</topic><topic>Drugs</topic><topic>Etiology</topic><topic>Fungi</topic><topic>Fungicides</topic><topic>Humans</topic><topic>in vitrostudies</topic><topic>Membranes</topic><topic>Microbial Sensitivity Tests</topic><topic>Microsporum - drug effects</topic><topic>Minimum inhibitory concentration</topic><topic>Monoterpenes</topic><topic>Monoterpenes - pharmacology</topic><topic>Multidrug resistance</topic><topic>Sensitivity</topic><topic>Synergism</topic><topic>Terbinafine</topic><topic>Terbinafine - pharmacology</topic><topic>Terpinolene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pinto, Â.V.</creatorcontrib><creatorcontrib>Oliveira, J.C.</creatorcontrib><creatorcontrib>Costa de Medeiros, C.A.</creatorcontrib><creatorcontrib>Silva, S.L.</creatorcontrib><creatorcontrib>Pereira, F.O.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Letters in applied microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pinto, Â.V.</au><au>Oliveira, J.C.</au><au>Costa de Medeiros, C.A.</au><au>Silva, S.L.</au><au>Pereira, F.O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes</atitle><jtitle>Letters in applied microbiology</jtitle><addtitle>Lett Appl Microbiol</addtitle><date>2021-03</date><risdate>2021</risdate><volume>72</volume><issue>3</issue><spage>292</spage><epage>298</epage><pages>292-298</pages><issn>0266-8254</issn><eissn>1472-765X</eissn><abstract>Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on mechanisms that confer multiple drug resistance. This study investigated the modulating activity of terbinafine promoted by dihydrojasmone and terpinolene against Microsporum canis LM 216, Trichophyton interdigitale H6 and T. interdigitale Δmdr2. The minimum inhibitory concentration (MIC) of test drugs was determined by broth microdilution. The effect of the drugs tested on plasma membrane functionality was analysed. Terbinafine MIC was determined in sub‐inhibitory concentrations of monoterpenes. Finally, it was performed an association study with terbinafine and monoterpenes. Dihydrojasmone presented lower MIC values than terpinolene. All fungi were sensitive to terbinafine, starting at 1 μg ml−1. All tested drugs increased K+ release (P < 0·05), affecting the functionality of the plasma membrane. Dihydrojasmone modulated the sensitivity of all strains against terbinafine, and terpinolene modulated the sensitivity of M. canis LM 216 and T. interdigitale Δmdr2. The monoterpenes and terbinafine drug associations presented synergism. In conclusion, the results suggest that the dihydrojasmone and terpinolene are promising antifungal agents that potentiate the antifungal activity of terbinafine against dermatophytes.
Significance and Impact of the Study: This is the first study that describes the dihydrojasmone and terpinolene action enhancing the antifungal activity of terbinafine against dermatophytes. In vitro tests have demonstrated that the monoterpenes act on the plasma membrane, positively modulating the sensitivity of fungal strains to terbinafine by a synergism association. We suggest that monoterpenes can be an effective and sustainable alternative while contributing to the reduction of the dermatophytes resistance to conventional drugs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32790923</pmid><doi>10.1111/lam.13371</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3081-4174</orcidid><orcidid>https://orcid.org/0000-0001-7168-7725</orcidid><orcidid>https://orcid.org/0000-0001-8426-2726</orcidid><orcidid>https://orcid.org/0000-0003-3240-8767</orcidid><orcidid>https://orcid.org/0000-0002-1257-2749</orcidid></addata></record> |
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| subjects | Antifungal activity Antifungal agents Antifungal Agents - pharmacology Arthrodermataceae - drug effects Cyclohexane Monoterpenes - pharmacology Dermatomycoses - drug therapy Dermatomycosis Dermatophytoses Drug delivery Drug resistance Drugs Etiology Fungi Fungicides Humans in vitrostudies Membranes Microbial Sensitivity Tests Microsporum - drug effects Minimum inhibitory concentration Monoterpenes Monoterpenes - pharmacology Multidrug resistance Sensitivity Synergism Terbinafine Terbinafine - pharmacology Terpinolene |
| title | Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes |
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