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

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

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 D5.5, 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 IC50 values ranging from 14 to 33 μM.

Original languageEnglish
Pages (from-to)4015-4023
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number20
DOIs
Publication statusPublished - 28 May 2012
Externally publishedYes

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