Relações entre a estrutura quimica de neolignanas e a sua atividade anti-leishmaniose, envolvendo calculos de solvatação

AUTOR(ES)
DATA DE PUBLICAÇÃO

1998

RESUMO

We continue to work on SAR analysis (Structure-Activity Relationships) of neolignans tested against visceral leishmaniasis; we initiated these studies in the middle of 1991. Conformational analysis of a series of 20 neolignans, 11 of which are inactivies and 9 are activies against leishmaniasis, was first performed. Then, phisico-chemical (PC) parameters were calculated in order to perform a SAR, using Pattern Recognition methods (PR). In order to obtain more informations about the relationships between the neolignan structures and their biological activity (BA) against leishmaniasis, a series of new PC parameters were included in the analysis. A significant improvement was obtained. It was possible to stablish a relative order of BA to the refered compounds. In the next step, the PR methods were compared with Multiple Linear Regression (MLR). The purpouse of the comparison was to investigate the aplicability of PR in SAR. The results confirmed that PR are capable of separating the compounds with higher BA of those with lower BA. Conformational analysis of neolignans was improved by taking account of the effects of solvent water on the compounds. We obtained some indication about the active conformation of the compounds. Comparisons between the local minima found to neolignans and the geometry of the other compounds that are activies in leishmaniasis, as well as studies about the geometry of arginine (a possible receptor of drugs activies against leishmaniasis), have confirmed our suposition about active conformation.

ASSUNTO(S)

estrutura quimica analise conformacional leishmaniose

ACESSO AO ARTIGO

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