{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:16:37Z","timestamp":1772759797985,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2013Brazil (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Azoles are the main antifungal agents employed in clinical practice to treat invasive candidiasis. Nonetheless, their efficacy is limited by fungal resistance mechanisms, mainly the overexpression of efflux pumps. Consequently, candidiasis has a worrisome death rate of 75%. One potential strategy to overcome efflux-mediated resistance is to inhibit this process. Ailanthus altissima is a Chinese tree that produces several active substances, including altissimacoumarin D. Due to the low yield of its extraction and the need to search for new drugs to treat candidiasis, this study aimed to synthesize altissimacoumarin D and its analogues, as well as evaluating their ability to reverse the resistance phenotype of Candida albicans. Coumarin isofraxidin was prepared via total synthesis through a solvent-free Knoevenagel condensation as the key step. Isofraxidin and other commercially available coumarins were alkylated with prenyl or geranyl groups to yield the natural product altissimacoumarin D and seven analogues. The antifungal activity of the coumarins and their ability to reverse the fungal resistance phenotype were assessed using microbroth methodologies. Toxicity was evaluated using erythrocytes and an in silico prediction. All compounds improved the antifungal activity of fluconazole by inhibiting efflux pumps, and ACS47 and ACS50 were the most active. None of the coumarins were toxic to erythrocytes. In silico predictions indicate that ACS47 and ACS50 may be safe for human use. ACS47 and ACS50 are promising candidates when used as adjuvants in the antifungal therapy against C. albicans-resistant strains.<\/jats:p>","DOI":"10.3390\/jof9070758","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T01:02:23Z","timestamp":1689728543000},"page":"758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans"],"prefix":"10.3390","volume":"9","author":[{"given":"Anna Claudia","family":"Silva","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, 508, Rio de Janeiro 21949-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Clemente","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Centro de Ci\u00eancias da Sa\u00fade, Bloco I, 44, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denilson Costa","family":"do Carmo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, 508, Rio de Janeiro 21949-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle Cristina Casaes","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, 508, Rio de Janeiro 21949-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-7999","authenticated-orcid":false,"given":"A.","family":"Ganesan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosangela Sabbatini Capella","family":"Lopes","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, 508, Rio de Janeiro 21949-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-8388","authenticated-orcid":false,"given":"Antonio","family":"Ferreira-Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Centro de Ci\u00eancias da Sa\u00fade, Bloco I, 44, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udio Cerqueira","family":"Lopes","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, 508, Rio de Janeiro 21949-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1128\/jcm.29.8.1702-1710.1991","article-title":"Genetic Dissimilarity of Commensal Strains of Candida Spp. Carried in Different Anatomical Locations of the Same Healthy Women","volume":"29","author":"Soll","year":"1991","journal-title":"J. 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