Design and synthesis of screening libraries based on the muurolane natural product scaffold

作者: Emma C. Barnes , Vanida Choomuenwai , Katherine T. Andrews , Ronald J. Quinn , Rohan A. Davis

DOI: 10.1039/C2OB00029F

关键词: Combinatorial chemistryEremophila PlantSmall Molecule LibrariesAmideChemistryHydrogen bondStructure–activity relationshipNatural productIc50 valuesScaffold

摘要: The plant-derived natural product 14-hydroxy-6,12-muuroloadien-15-oic acid (1) was identified as a unique scaffold that could be chemically elaborated to generate novel lead- or drug-like screening libraries. Prior synthesis virtual library generated and prioritised based on physicochemical parameters such log P, D5.5, hydrogen bond donors/acceptors, molecular weight. isolated from the endemic Australian plant Eremophila mitchellii then utilised in parallel solution-phase generation of two series analogues. first consisted six semi-synthetic amide derivatives, whilst second contained carbamate These libraries have been evaluated for antimalarial activity using chloroquine-sensitive Plasmodium falciparum line (3D7) several compounds displayed low moderate with IC50 values ranging 14 33 μM.

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