Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.
ChemMedChem
; 11(1): 38-42, 2016 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-26486566
ABSTRACT
Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
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Inibidores Enzimáticos
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Descoberta de Drogas
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Mycobacterium tuberculosis
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Antituberculosos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article