title: Strategies in the discovery of novel antifungal scaffolds.
abstract: The development of next-generation antifungal agents with novel chemical scaffolds and new mechanisms of action is vital due to increased incidence and mortality of invasive fungal infections and severe drug resistance. This review will summarize current strategies to discover novel antifungal scaffolds. In particular, high-throughput screening, drug repurposing, antifungal natural products and new antifungal targets are focused on. New scaffolds with validated antifungal activity, their discovery and optimization process as well as structure-activity relationships are discussed in detail. Perspectives that could inspire future antifungal drug discovery are provided.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, Nanjing, 210002, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D055808:Drug Discovery; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009181:Mycoses / Q000188:drug therapy*
chemical_list: D000935:Antifungal Agents
keywords: antifungal drug resistance; antifungal lead compounds; drug repurposing; fungal biofilm inhibitors; invasive fungal infections; new antifungal scaffolds; strategies in antifungal drug discovery