ABSTRACT
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.
Subject(s)
Anthelmintics/pharmacology , Lignans/pharmacology , Piper/chemistry , Plant Extracts/pharmacology , Schistosoma mansoni/drug effects , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Density Functional Theory , Female , Lignans/chemistry , Lipids/chemistry , Male , Mice, Inbred BALB C , Models, Theoretical , Molecular Docking Simulation , Molecular Structure , Parasite Egg Count , Plant Extracts/chemistry , Proton Magnetic Resonance Spectroscopy , Schistosoma mansoni/chemistry , Static Electricity , Tubulin/chemistryABSTRACT
This article reports on the in vitro activity of the hydroalcoholic extract of Pfaffia glomerata roots, its hydrolyzed fractions, and pfaffic acid against Trypanosoma cruzi. The hydroalcoholic extract obtained from dried, milled P. glomerata roots was submitted to acid hydrolysis followed by partition with CHCl3 . The concentrated CHCl3 fraction was suspended in MeOH/H2 O and partitioned with hexane (F1), CHCl3 (F2), and AcOEt (F3), in this sequence. The trypanocidal activity of the hydrolyzed extract and its fractions was evaluated in vitro. The hydroalcoholic extract displayed low activity, but fraction F1 was active against trypomastigotes of the Y strain of T. cruzi, with IC50 = 47.89 µg/ml. The steroids campesterol (7.7%), stigmasterol (18.7%), ß-sitosterol (16.8%), Δ7 -stigmastenol (4.6%), and Δ7 -spinasterol (7.5%) were the major constituents of F1, along with fatty acid esters (7.6%) and eight aliphatic hydrocarbons (30.1%). Fractions F2 and F3 exhibited moderate activity, and pfaffic acid, one of the main chemical constituents of these fractions, displayed IC50 = 44.78 µm (21.06 µg/ml). On the other hand, the hydroalcoholic extract of P. glomerata roots, which is rich in pfaffosides, was inactive. Therefore, the main aglycone of pfaffosides, pfaffic acid, is much more active against trypomastigotes of the Y strain of T. cruzi than its corresponding glycosides and should be further investigated.