RESUMO
Conformational analysis of marchantin A (1), a bis(diarylether) type, and riccardin A (2), a diarylether-biphenyl type macrocyclic bis(bibenzyl) was carried out by systematic unbounded multiple minimum search (SUMM). Mobility of the macrocyclic rings was analysed by variable temperature 1H-NMR study. Molecular similarity analysis was performed on the minimum energy conformers of 1 and 2 comparing their steric, electrostatic and hydrophobic properties. Correlation between complexation properties and calmodulin inhibitor activity was established. Differences in steric and electrostatic profiles may be responsible for the reduced Ca2+ affinity and activity of 2.
Assuntos
Bibenzilas/química , Catecóis/química , Éteres Cíclicos/química , Modelos Moleculares , Éteres Fenílicos/química , Simulação por Computador , Espectroscopia de Ressonância Magnética , Relação Estrutura-AtividadeRESUMO
The biological activities reported for marchantin A (1), a natural cyclic bis(bibenzyl), were studied in comparison with cepharanthine (2), a therapeutically useful bisbenzylisoquinoline alkaloid. Based on the examination of steric, electrostatic, and hydrophobic similarity, as well as on the comparison of biological activities, the similar therapeutic properties of 1 and 2 can be attributed to binding on a common receptor. The wide range of activity of 1 can be interpreted by a mechanism of action based on a calcium binding.
