{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:54:32Z","timestamp":1790834072426,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (<jats:italic>S<\/jats:italic>)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (<jats:italic>S<\/jats:italic>)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.<\/jats:p>","DOI":"10.1128\/aac.01657-10","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T06:10:11Z","timestamp":1310451011000},"page":"4789-4801","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives"],"prefix":"10.1128","volume":"55","author":[{"given":"Anke","family":"Burger-Kentischer","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Finkelmeier","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Keller","sequence":"additional","affiliation":[{"name":"Institute for Interfacial Engineering, University Stuttgart, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Bauer","sequence":"additional","affiliation":[{"name":"EMC Microcollections GmbH, T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"EMC Microcollections GmbH, T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Kleymann","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Biochemistry, University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Abu Rayyan","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology und Infection Medicine, University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Singh","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology und Infection Medicine, University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schr\u00f6ppel","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology und Infection Medicine, University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Lemuth","sequence":"additional","affiliation":[{"name":"Institute for Interfacial Engineering, University Stuttgart, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Wiesm\u00fcller","sequence":"additional","affiliation":[{"name":"EMC Microcollections GmbH, T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Rupp","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1688-1694.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn764"},{"key":"e_1_3_2_4_2","article-title":"High-throughput screening-based identification and structure-activity relationship-characterization defined (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole as a highly antimycotic agent, non-toxic to cell lines","author":"Bauer J.","unstructured":"BauerJ. . 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