Topliss method in the optimization of salicylic acid derivatives as potential antimycobacterial agents

Nenhuma Miniatura disponível

Data

2008-02-01

Orientador

Coorientador

Pós-graduação

Curso de graduação

Título da Revista

ISSN da Revista

Título de Volume

Editor

Blackwell Publishing

Tipo

Artigo

Direito de acesso

Acesso restrito

Resumo

The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett's sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B-4 and molecular volume) were considered to elucidate structure-activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs.

Descrição

Idioma

Inglês

Como citar

Chemical Biology & Drug Design. Oxford: Blackwell Publishing, v. 71, n. 2, p. 167-172, 2008.

Itens relacionados

Financiadores