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Table Of Contents

The Rate-Limiting Steps of Antibacterial Discovery
The Multitarget Hypothesis
ANTIBACTERIAL RESISTANCE
Endogenous versus Exogenous Resistance
Assessing Endogenous Resistance Potential
Fitness of Resistant Mutants and Compensatory Mutations
TARGETS
Linking MIC to Target Inhibition
Support for Enzyme Inhibition as the Antibacterial Mechanism
RECENT RECORD OF SINGLE-ENZYME- TARGETED AGENTS
The Opacity of the Discovery Process
MurB to MurF Enzymes as Antibacterial Targets
Targets of Inhibitors Discovered by Enzyme Screening or Design
Inhibitors Identified after Phenotypic and Empirical Discovery
Single-Enzyme Targets of Novel Inhibitors in Clinical Trials
Summary of Challenges of Single-Target Discovery
MULTITARGETING
Single Pharmacophore, Multiple Targets
Targeting Substrates and Cofactors
Hybrid Molecules: Dual Pharmacophore, Multiple Targets
CHEMISTRY
Spectrum Is Due to Permeability as Well as Target Distribution
Chemical Libraries Are Limiting
Barriers to Intracellular Accumulation in Gram-Negative Organisms
Formulation of Rules for Intracellular Accumulation
Dealing with Efflux
A BRIEF PRESCRIPTION FOR NATURAL PRODUCT SCREENING
CONCLUSIONS
REFERENCES
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Clin. Microbiol Rev. 2011 Silver 71 109

Clin. Microbiol Rev. 2011 Silver 71 109

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Published by Swarup De

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Published by: Swarup De on Feb 23, 2012
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