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The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current antifungal drugs target the fungal cell membrane, cell wall, or intracellular components, but resistance mechanisms such as altered drug\u2010target interactions, enhanced efflux, and adaptive cellular responses have diminished their efficacy. Recent research has highlighted the potential of dual inhibitors that simultaneously target multiple pathways or enzymes involved in fungal growth and survival. Combining pharmacophores, such as lanosterol 14\u03b1\u2010demethylase (CYP51), heat shock protein 90 (HSP90), histone deacetylase (HDAC), and squalene epoxidase (SE) inhibitors, has led to the development of compounds with enhanced antifungal activity and reduced resistance. This dual\u2010target approach, along with novel chemical scaffolds, not only represents a promising strategy for combating antifungal resistance but is also being utilized in the development of anticancer agents. This review explores the development of new antifungal agents that employ mono\u2010, dual\u2010, or multi\u2010target strategies to combat IFIs. We discuss emerging antifungal targets, resistance mechanisms, and innovative therapeutic approaches that offer hope in managing these challenging infections.<\/jats:p>","DOI":"10.1111\/cbdd.70045","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T13:10:39Z","timestamp":1737551439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Significance of Mono\u2010 and Dual\u2010Effective Agents in the Development of New Antifungal Strategies"],"prefix":"10.1111","volume":"105","author":[{"given":"Cengiz","family":"Zobi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Erzincan Binali Yildirim University  Erzincan Turkiye"},{"name":"Department of \u0130li\u00e7 Dursun Yildirim MYO Erzincan Binali Yildirim University  Erzincan Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5685-7511","authenticated-orcid":false,"given":"Oztekin","family":"Algul","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Erzincan Binali Yildirim University  Erzincan Turkiye"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Mersin University  Mersin Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.17.2659"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/JAC\/DKAA382"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz020"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00973\u201015"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab431"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15051365"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12281\u2010023\u201000451\u20107"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6020066"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2007.11.005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.0c00096"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2024.01.012"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"Alkhazraji S. 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