Molecular descriptors calculation as a tool in the analysis of the antileishmanial activity achieved by two series of diselenide derivatives. An insight into its potential action mechanism.
J Mol Graph Model
; 60: 63-78, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26119983
ABSTRACT
A molecular modeling study has been carried out on two previously reported series of symmetric diselenide derivatives that show remarkable antileishmanial in vitro activity against Leishmania infantum intracellular amastigotes and in infected macrophages (THP-1 cells), in addition to showing favorable selectivity indices. Series 1 consists of compounds that can be considered as central scaffold constructed with a diaryl/dialkylaryl diselenide central nucleus, decorated with different substituents located on the aryl rings. Series 2 consists of compounds constructed over a diaryl diselenide central nucleus, decorated in 4 and 4' positions with an aryl or heteroaryl sulfonamide fragment, thus forming the diselenosulfonamide derivatives. With regard to the diselenosulfonamide derivatives (2 series), the activity can be related, as a first approximation, with (a) the ability to release bis(4-aminophenyl) diselenide, the common fragment which can be ultimately responsible for the activity of the compounds. (b) the anti-parasitic activity achieved by the sulfonamide pharmacophore present in the analyzed derivatives. The data that support this connection include the topography of the molecules, the conformational behavior of the compounds, which influences the bond order, as well as the accessibility of the hydrolysis point, and possibly the hydrophobicity and polarizability of the compounds.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Modelos Moleculares
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Compostos Organosselênicos
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Leishmania infantum
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Antiprotozoários
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article