Topliss method in the optimization of salicylic acid derivatives as potential antimycobacterial agents
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Data
2008-02-01
Autores
da Silva, Marcia [UNESP]
Souza Menezes, Carla Maria
Ferreira, Elizabeth Igne
Leite, Clarice Queico Fujimura [UNESP]
Sato, Daisy Nakamura
Correia, Cristiane Cardoso [UNESP]
Pimenta, Carolina Pereira [UNESP]
Alves Botelho, Katia Cirlene
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Editor
Blackwell Publishing
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.
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antimycobacterial, p-aminosalicylic acid, salicylic acid, Topliss, tuberculostatic
Como citar
Chemical Biology & Drug Design. Oxford: Blackwell Publishing, v. 71, n. 2, p. 167-172, 2008.