title: Design and synthesis of screening libraries based on the muurolane natural product scaffold.
abstract: 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 to synthesis a virtual library was generated and prioritised based on drug-like physicochemical parameters such as log P, log D(5.5), hydrogen bond donors/acceptors, and molecular weight. The natural product scaffold (1) was isolated from the endemic Australian plant Eremophila mitchellii and then utilised in the parallel solution-phase generation of two series of analogues. The first library consisted of six semi-synthetic amide derivatives, whilst the second contained six carbamate analogues. These libraries have been evaluated for antimalarial activity using a chloroquine-sensitive Plasmodium falciparum line (3D7) and several compounds displayed low to moderate activity with IC(50) values ranging from 14 to 33 μM.
authors.affiliation: Eskitis Institute, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Barnes
authors.forename: Vanida
authors.initials: V
authors.lastname: Choomuenwai
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Andrews
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry*; D041621:Eremophila Plant / Q000737:chemistry*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D054852:Small Molecule Libraries