RESUMO
Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value.
Assuntos
Anti-Helmínticos/farmacologia , Lignanas/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Teoria da Densidade Funcional , Feminino , Lignanas/química , Lipídeos/química , Masculino , Camundongos Endogâmicos BALB C , Modelos Teóricos , Simulação de Acoplamento Molecular , Estrutura Molecular , Contagem de Ovos de Parasitas , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Schistosoma mansoni/química , Eletricidade Estática , Tubulina (Proteína)/químicaRESUMO
A set of seven diterpenes, three kauranes and four trachylobanes, isolated from the African plant Psiadia punctulata were assayed against Mycobacterium tuberculosis and reached activity comparable with cycloserine, a second line drug used to treat tuberculosis (TB). Several structural properties of those diterpenes, such as lipophilicity, HOMO and LUMO energies, charge density, and intramolecular hydrogen bond (IHB) formation, were obtained by theoretical calculations and compared with their activities. Peculiar correlations were observed, especially between activity, lipophilicity and IHB formation.