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• W2900631499 abstract "Abstract Selective and specific inhibitors of Plasmodium falciparum lysyl‐tRNA synthetase represent promising therapeutic antimalarial avenues. Cladosporin was identified as a potent P. falciparum lysyl‐tRNA synthetase inhibitor, with an activity against parasite lysyl‐tRNA synthetase >100‐fold more potent than that of the activity registered against the human enzyme. Despite its compelling activity, cladosporin exhibits poor oral bioavailability; a critical requirement for antimalarial drugs. Thus, the quest to develop metabolically stable cladosporin‐derived analogues, while retaining similar selectivity and potency to that of the natural compound, has begun. Chemogenomic profiling of a designed library allowed an entirely innovative structure–activity relationship study to be initiated; this shed light on structural evidence of a privileged scaffold with a unique activity against tRNA synthetases." @default.
• W2900631499 created "2018-11-29" @default.
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• W2900631499 date "2019-02-04" @default.
• W2900631499 modified "2023-10-09" @default.
• W2900631499 title "Design and Synthesis of Metabolically Stable tRNA Synthetase Inhibitors Derived from Cladosporin" @default.
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• W2900631499 doi "https://doi.org/10.1002/cbic.201800587" @default.
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