{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:43:39Z","timestamp":1788993819415,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science and Technological Development of Republic of Serbia","award":["173032"],"award-info":[{"award-number":["173032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The prevalence of invasive fungal infections has been dramatically increased as the size of the immunocompromised population worldwide has grown. Aspergillus fumigatus is characterized as one of the most widespread and ubiquitous fungal pathogens. Among antifungal drugs, azoles have been the most widely used category for the treatment of fungal infections. However, increasingly, azole-resistant strains constitute a major problem to be faced. Towards this direction, our study focused on the identification of compounds bearing novel structural motifs which may evolve as a new class of antifungals. To fulfil this scope, a combination of in silico techniques and in vitro assays were implemented. Specifically, a ligand-based pharmacophore model was created and served as a 3D search query to screen the ZINC chemical database. Additionally, molecular docking and molecular dynamics simulations were used to improve the reliability and accuracy of virtual screening results. In total, eight compounds, bearing completely different chemical scaffolds from the commercially available azoles, were proposed and their antifungal activity was evaluated using in vitro assays. Results indicated that all tested compounds exhibit antifungal activity, especially compounds 1, 2, and 4, which presented the most promising minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values and, therefore, could be subjected to further hit to lead optimization.<\/jats:p>","DOI":"10.3390\/molecules24213853","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T11:05:18Z","timestamp":1572001518000},"page":"3853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Novel Hit Compounds as Putative Antifungals: The Case of Aspergillus fumigatus"],"prefix":"10.3390","volume":"24","author":[{"given":"Eftichia","family":"Kritsi","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4642-8163","authenticated-orcid":false,"given":"Minos-Timotheos","family":"Matsoukas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Patras, 26504 Patras, Greece"},{"name":"Cloudpharm, Monumental Plaza, Building C, 44, Kifissias Avenue, Marousi, 15125 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Potamitis","sequence":"additional","affiliation":[{"name":"Cloudpharm, Monumental Plaza, Building C, 44, Kifissias Avenue, Marousi, 15125 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8325-2980","authenticated-orcid":false,"given":"Anastasia","family":"Detsi","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, National Technical University of Athens, 9, Iroon-Polytechneiou-Str, 15773 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-5490","authenticated-orcid":false,"given":"Marija","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d- National Institute of Republic of Serbia, University of Belgrade, 142, Bulevar Despota Stefana, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-756X","authenticated-orcid":false,"given":"Marina","family":"Sokovic","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d- National Institute of Republic of Serbia, University of Belgrade, 142, Bulevar Despota Stefana, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-6078","authenticated-orcid":false,"given":"Panagiotis","family":"Zoumpoulakis","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ikeh, M., Ahmed, Y., and Quinn, J. (2017). Phosphate acquisition and virulence in human fungal pathogens. Microorganisms, 5.","DOI":"10.3390\/microorganisms5030048"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrd.2017.46","article-title":"The antifungal pipeline: A reality check","volume":"16","author":"Perfect","year":"2017","journal-title":"Nat. Rev. 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