Issue 20, 2012

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 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.

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

Supplementary files

Article information

Article type
Paper
Submitted
05 Jan 2012
Accepted
20 Feb 2012
First published
15 Mar 2012

Org. Biomol. Chem., 2012,10, 4015-4023

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

E. C. Barnes, V. Choomuenwai, K. T. Andrews, R. J. Quinn and R. A. Davis, Org. Biomol. Chem., 2012, 10, 4015 DOI: 10.1039/C2OB00029F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements