Rationalising the inhibition of M. tuberculosis MshB by a series of inhibitors constructed from plumbagin conjugated via a viariable alkyl linker to a phenyl thioglycoside

Rogers, Ian L

Rationalising the inhibition of M. tuberculosis MshB by a series of inhibitors constructed from plumbagin conjugated via a viariable alkyl linker to a phenyl thioglycoside

Master Thesis

2011

Publisher

University of Cape Town

Department

Department of Chemistry

Faculty

Faculty of Science

Abstract

Infection by M. tuberculosis results in an estimated 1.7 million TB related deaths worldwide. Mycothiol is produced in M. tuberculosis as the dominant low molecular weight thiol and is thought to protect the bacteria against oxidative stress. Since mycothiol is unique to Actinomycetes and is also proposed to play an important role in the dormant state of Mycobacteria, the pseudo-dissacharide is seen as a potential target for novel anti-tuberculars. Targeting the mycothiol redox cycle has led to MshB inhibition by a series of substrate analogues. Kinetics studied showed that the competitive inhibition increased when the alkyl linker was lengthened. The binding of the inhibitors was investigated using computational techniques in order to rationalise the observed trend in inhibition.

Keywords

Chemistry

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