{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:06:18Z","timestamp":1780581978922,"version":"3.54.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The ability of dermatophytes to develop biofilms in host tissues confers physical and biochemical resistance to antifungal drugs. Therefore, research to find new compounds against dermatophyte biofilm is crucial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the antifungal activity of riparin II (RIP2), nor-riparin II (NOR2) and dinor-riparin II (DINOR2) against Trichophyton rubrum, Microsporum canis and Nannizzia gypsea strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Initially, we determined the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of benzamides. We evaluated the inhibitory effects on the development of dermatophyte biofilms using in vitro and ex vivo models. Finally, we built three-dimensional models of the sulphite pump Ssu1 to investigate the interactions with the benzamides by molecular docking.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>RIP2 showed a broad spectrum of activity against T. rubrum, M. canis and N. gypsea, whereas NOR2 and DINOR2 were more selective. Furthermore, the shortening of the carbon chain from RIP2 benzamide to NOR2 and DINOR2 homologs caused a decrease in the MIC values. The benzamides reduced biofilm production and viability in vitro (P &amp;lt; 0.05) at MIC. This result was similar ex vivo in human nail fragments tests, but NOR2 and DINOR2 showed significant results at 2xMIC (P &amp;lt; 0.05). We constructed a model of the Ssu1 protein for each dermatophyte with high similarity. Molecular docking showed that the benzamides obtained higher binding energy values than ciclopirox.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study shows the antibiofilm potential for riparin II-type benzamides as new drugs targeting dermatophytes by inhibiting the Ssu1 protein.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae013","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T07:12:08Z","timestamp":1706771528000},"page":"617-631","source":"Crossref","is-referenced-by-count":8,"title":["Riparin II-type benzamides as novel antibiofilm agents against dermatophytes: chemical synthesis, <i>in vitro<\/i>, <i>ex vivo<\/i> and <i>in silico<\/i> evaluation"],"prefix":"10.1093","volume":"79","author":[{"given":"Marcelo Ant\u00f4nio N\u00f3brega da","family":"Rocha","sequence":"first","affiliation":[{"name":"Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande , Cuit\u00e9 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel Pereira","family":"Silva","sequence":"additional","affiliation":[{"name":"Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande , Cuit\u00e9 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risley Nikael Medeiros","family":"Silva","sequence":"additional","affiliation":[{"name":"Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande , Cuit\u00e9 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Ribeiro de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Department of Pharmaceutical Sciences, Federal University of Paraiba , Jo\u00e3o Pessoa , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Maria","family":"Barbosa-Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Department of Pharmaceutical Sciences, Federal University of Paraiba , Jo\u00e3o Pessoa , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara dos Santos","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Federal University of Para\u00edba , Jo\u00e3o Pessoa , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Shellygton","family":"Lima","sequence":"additional","affiliation":[{"name":"Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande , Cuit\u00e9 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jailton","family":"de Souza-Ferrari","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Paraiba , Jo\u00e3o Pessoa , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3081-4174","authenticated-orcid":false,"given":"Fillipe de Oliveira","family":"Pereira","sequence":"additional","affiliation":[{"name":"Fungi Research Group, Academic Unit of Health in the Education and Health Center, Federal University of Campina Grande , Cuit\u00e9 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"2024030105172815900_dkae013-B1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1099\/jmm.0.000982","article-title":"Host- and pathogen-dependent susceptibility and predisposition to dermatophytosis","volume":"68","author":"Gnat","year":"2019","journal-title":"J Med Microbiol"},{"key":"2024030105172815900_dkae013-B2","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s11046-017-0194-9","article-title":"Human infections with Microsporum gypseum complex (Nannizzia gypsea) in Slovenia","volume":"182","author":"Dolenc-Volj\u010d","year":"2017","journal-title":"Mycopathologia"},{"key":"2024030105172815900_dkae013-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jmm.0.001321","article-title":"The prevalence of dermatophytoses in Brazil: a systematic review","volume":"70","author":"De Oliveira Pereira","year":"2021","journal-title":"J Med Microbiol"},{"key":"2024030105172815900_dkae013-B4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/mmy\/myac058","article-title":"Reactive oxygen and nitrogen species are crucial for the antifungal activity of amorolfine and ciclopirox olamine against the dermatophyte Trichophyton interdigitale","volume":"60","author":"Carmo","year":"2022","journal-title":"Med Mycol"},{"key":"2024030105172815900_dkae013-B5","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.jdcr.2020.05.025","article-title":"Treatment-resistant dermatophytosis: a representative case highlighting an emerging public health threat","volume":"6","author":"Gu","year":"2020","journal-title":"JAAD Case Rep"},{"key":"2024030105172815900_dkae013-B6","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"2024030105172815900_dkae013-B7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3390\/jof8010039","article-title":"Pathogenesis, immunology and management of dermatophytosis","volume":"8","author":"Jartarkar","year":"2021","journal-title":"J Fungi"},{"key":"2024030105172815900_dkae013-B8","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1016\/S0031-9422(00)83890-X","article-title":"Benzoyl esters and amides, styrylpyrones and neolignans from the fruits of Aniba riparia","volume":"26","author":"Barbosa-Filho","year":"1987","journal-title":"Phytochemistry"},{"key":"2024030105172815900_dkae013-B9","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1248\/bpb.30.1212","article-title":"Evaluation of effects of N-(2-hydroxybenzoyl) tyramine (riparin II) from Aniba riparia (NEES) MEZ (Lauracea) in anxiety models in mice","volume":"30","author":"De Sousa","year":"2007","journal-title":"Biol Pharm Bull"},{"key":"2024030105172815900_dkae013-B10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1472-8206.2011.00973.x","article-title":"Antidepressant-like effect of riparin II from Aniba riparia in mice: evidence for the involvement of the monoaminergic system","volume":"27","author":"Teixeira","year":"2013","journal-title":"Fundam Clin Pharmacol"},{"key":"2024030105172815900_dkae013-B11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cbi.2018.04.003","article-title":"Antinociceptive activity of riparin II from Aniba riparia: further elucidation of the possible mechanisms","volume":"287","author":"Rodrigues de Carvalho","year":"2018","journal-title":"Chem Biol Interact"},{"key":"2024030105172815900_dkae013-B12","doi-asserted-by":"crossref","first-page":"104529","DOI":"10.1016\/j.micpath.2020.104529","article-title":"Antimicrobial activity and biofilm inhibition of riparins I, II and III and ultrastructural changes in multidrug-resistant bacteria of medical importance","volume":"149","author":"Oliveira-J\u00fanior","year":"2020","journal-title":"Microb Pathog"},{"key":"2024030105172815900_dkae013-B13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuint.2018.07.007","article-title":"Riparin II ameliorates corticosterone-induced depressive-like behavior in mice: role of antioxidant and neurotrophic mechanisms","volume":"120","author":"Lopes","year":"2018","journal-title":"Neurochem Int"},{"key":"2024030105172815900_dkae013-B14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cbi.2013.07.007","article-title":"Evaluation of the anti-inflammatory activity of riparin II (O-methil-N-2-hidroxi-benzoyl tyramine) in animal models","volume":"205","author":"De Carvalho","year":"2013","journal-title":"Chem Biol Interact"},{"key":"2024030105172815900_dkae013-B15","first-page":"332","article-title":"Synthesis of several new phenylethylamines of substituted benzoic acids","volume":"13","author":"Barbosa-Filho","year":"1990","journal-title":"Quim Nova"},{"key":"2024030105172815900_dkae013-B16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3390\/jof9020231","article-title":"Antifungal and antibiofilm activity of riparin III against dermatophytes","volume":"9","author":"Silva","year":"2023","journal-title":"J Fungi"},{"key":"2024030105172815900_dkae013-B17","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/00275514.2023.2170209","article-title":"In vitro and ex vivo antibiofilm activity of riparin 1, and its nor and dinor homologs, against dermatophytes","volume":"115","author":"Medeiros Silva","year":"2023","journal-title":"Mycologia"},{"key":"2024030105172815900_dkae013-B18","first-page":"291","article-title":"A new group of potential antitubercular agents: antimycobacterial N-benzylsalicylamides","volume":"52","author":"Waisser","year":"2003","journal-title":"Ceska Slov Farm"},{"key":"2024030105172815900_dkae013-B19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3109\/14756361003671060","article-title":"Synthesis and antiproliferative activities against Hep-G2 of salicylanide derivatives: potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase","volume":"26","author":"Zhu","year":"2011","journal-title":"J Enzyme Inhib Med Chem"},{"key":"2024030105172815900_dkae013-B20","volume-title":"M38 Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi","author":"CLSI C& LSI","year":"2017"},{"key":"2024030105172815900_dkae013-B21","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s12223-011-0049-6","article-title":"Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism","volume":"56","author":"de Quadros","year":"2011","journal-title":"Folia Microbiol (Praha)"},{"key":"2024030105172815900_dkae013-B22","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/S0190-9622(98)70482-7","article-title":"Fungicidal versus fungistatic activity of terbinafine and itraconazole: an in vitro comparison","volume":"38","author":"Hazen","year":"1998","journal-title":"J Am Acad Dermatol"},{"key":"2024030105172815900_dkae013-B23","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/myc.12763","article-title":"In vitro activity of azole derivatives and griseofulvin against planktonic and biofilm growth of clinical isolates of dermatophytes","volume":"61","author":"Brilhante","year":"2018","journal-title":"Mycoses"},{"key":"2024030105172815900_dkae013-B24","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1080\/08927014.2014.919282","article-title":"In vitro characterization of Trichophyton rubrum and T. mentagrophytes biofilms","volume":"30","author":"Costa-Orlandi","year":"2014","journal-title":"Biofouling"},{"key":"2024030105172815900_dkae013-B25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/mmy\/myu081","article-title":"Candida tropicalis isolates obtained from veterinary sources show resistance to azoles and produce virulence factors","volume":"53","author":"Cordeiro","year":"2015","journal-title":"Med Mycol"},{"key":"2024030105172815900_dkae013-B26","doi-asserted-by":"crossref","first-page":"37867","DOI":"10.1038\/srep37867","article-title":"Hydroxychavicol: a phytochemical targeting cutaneous fungal infections","volume":"6","author":"Ali","year":"2016","journal-title":"Sci Rep"},{"key":"2024030105172815900_dkae013-B27","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.3389\/fmicb.2019.01228","article-title":"In vitro evaluation of photodynamic effects against biofilms of dermatophytes involved in onychomycosis","volume":"10","author":"Chen","year":"2019","journal-title":"Front Microbiol"},{"key":"2024030105172815900_dkae013-B28","doi-asserted-by":"crossref","first-page":"D46","DOI":"10.1093\/nar\/gkp1024","article-title":"GenBank","volume":"38","author":"Benson","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2024030105172815900_dkae013-B29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/pro.3290","article-title":"Clustal Omega for making accurate alignments of many protein sequences","volume":"27","author":"Sievers","year":"2018","journal-title":"Protein Sci"},{"key":"2024030105172815900_dkae013-B30","first-page":"8","volume-title":"O Programa BLAST: Utiliza\u00e7\u00e3o Para Estudos de Recursos Gen\u00e9ticos e Biotecnologia","author":"Amaral","year":"2007"},{"key":"2024030105172815900_dkae013-B31","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: new development for protein structure and function predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2024030105172815900_dkae013-B32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1472-6807-5-14","article-title":"The Ramachandran plots of glycine and pre-proline","volume":"5","author":"Ho","year":"2005","journal-title":"BMC Struct Biol"},{"key":"2024030105172815900_dkae013-B33","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1515\/bmc.2010.022","article-title":"A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins","volume":"1","author":"Hollingsworth","year":"2010","journal-title":"Biomol Concepts"},{"key":"2024030105172815900_dkae013-B34","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1110\/ps.03235203","article-title":"Revisiting the Ramachandran plot: hard-sphere repulsion, electrostatics, and H-bonding in the \u03b1-helix","volume":"12","author":"Ho","year":"2009","journal-title":"Protein Sci"},{"key":"2024030105172815900_dkae013-B35","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0022-2836(63)80023-6","article-title":"Stereochemistry of polypeptide chain configurations","volume":"7","author":"Ramachandran","year":"1963","journal-title":"J Mol Biol"},{"key":"2024030105172815900_dkae013-B36","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"2024030105172815900_dkae013-B37","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/prot.10465","article-title":"Improved protein-ligand docking using GOLD","volume":"52","author":"Verdonk","year":"2003","journal-title":"Proteins"},{"key":"2024030105172815900_dkae013-B38","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1590\/S0103-50532011001100023","article-title":"DBU as a catalyst for the synthesis of amides via aminolysis of methyl esters","volume":"22","author":"De Lima","year":"2011","journal-title":"J Braz Chem Soc"},{"key":"2024030105172815900_dkae013-B39","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3998\/ark.5550190.0011.816","article-title":"Evolution of amide bond formation","volume":"2010","author":"Joullie","year":"2010","journal-title":"Arkivoc"},{"key":"2024030105172815900_dkae013-B40","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.drudis.2015.01.009","article-title":"An analysis of FDA-approved drugs: natural products and their derivatives","volume":"21","author":"Patridge","year":"2016","journal-title":"Drug Discov Today"},{"key":"2024030105172815900_dkae013-B41","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s00253-015-7262-1","article-title":"Microbial decomposition of keratin in nature\u2014a new hypothesis of industrial relevance","volume":"100","author":"Lange","year":"2016","journal-title":"Appl Microbiol Biotechnol"},{"key":"2024030105172815900_dkae013-B42","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1038\/jid.2013.41","article-title":"Keratin degradation by dermatophytes relies on cysteine dioxygenase and a sulfite efflux pump","volume":"133","author":"Grumbt","year":"2013","journal-title":"J Invest Dermatol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/3\/617\/56796795\/dkae013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/3\/617\/56796795\/dkae013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T05:19:24Z","timestamp":1709270364000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/3\/617\/7595473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,1,31]]},"published-print":{"date-parts":[[2024,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae013","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2024,1,31]]}}}