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
(-)-Hinokinin (1) is a dibenzylbutyrolactone lignan obtained by the partial synthesis of (-)-cubebin. This study reports the antigenotoxic and anticarcinogenic potential of 1 by the comet and aberrant crypt focus assays in the peripheral blood and colon of 4-5-week-old Wistar rats, respectively. The rats were exposed to 1,2-dimethylhydrazine (40 mg/kg) and were treated by gavage with doses of 10, 20, and 40 mg/kg of 1. The results showed that the dose of 40 mg/kg was neither genotoxic nor carcinogenic. In the comet assay, all 1 doses displayed antigenotoxic effects. In addition, this compound (20 and 40 mg/kg) exhibited an anticarcinogenic effect in the aberrant crypt focus assay.
Subject(s)
1,2-Dimethylhydrazine/pharmacology , 4-Butyrolactone/analogs & derivatives , Dioxoles/pharmacology , Lignans/pharmacology , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Animals , Anticarcinogenic Agents/pharmacology , Benzodioxoles , Carcinogens/pharmacology , Colon/drug effects , Comet Assay , DNA Damage/drug effects , Dimethylhydrazines/chemistry , Dioxoles/chemistry , Lignans/chemistry , Male , Molecular Structure , Piper/chemistry , Rats , Rats, Wistar , StereoisomerismABSTRACT
Chemical investigation of the EtOAc fraction (EF) obtained from the ethanolic extract of Zanthoxylum naranjillo (Rutaceae) leaves (EE) by preparative HPLC resulted in the isolation of protocatechuic acid (1), gallic acid (2), p-hydroxybenzoic acid (3), and 5-O-caffeoylshikimic acid (4). This is the first time that the presence of compounds 1-4 in Z. naranjillo has been reported. Compounds 1-4, the EE, and EF were tested in vitro against Schistosoma mansoni adult worms. The results showed that the S. mansoni daily egg production decreased by 29.8%, 13.5%, 28.4%, 17.7%, 16.3%, and 6.4%, respectively. Compounds 1 and 3 were also able to separate adult worm pairs into male and female. This activity may be correlated with the reduction in egg production, since 1 and 3 showed better inhibitory properties compared with 2 and 4.
Subject(s)
Schistosoma mansoni/drug effects , Schistosomicides/isolation & purification , Zanthoxylum/chemistry , Animals , Female , Male , Mice , Mice, Inbred BALB C/parasitology , Motor Activity/drug effects , Oviposition/drug effects , Plant Leaves/chemistry , Schistosoma mansoni/growth & development , Schistosoma mansoni/physiology , Schistosomicides/pharmacologyABSTRACT
Seven tetrahydrofuran lignans, isolated from Nectandra megapotamica (Lauraceae), were evaluated for their in vitro antileishmanial and antimalarial activities. Among the evaluated compounds, machilin-G (1a) and veraguensin (2a) showed the highest antileishmanial activities, displaying for both compounds an IC(50) value of 18 microg/mL and an IC(90) value of 36 microg/mL, while galgravin (1b), nectandrin-A (1c), nectandrin-B (1d), calopeptin (2b) and ganshisandrine (3) were inactive against Leishmania donovani. In the antimalarial assay against Plasmodium falciparum, it was observed that calopeptin (2b) displayed moderate activity, with IC(50) values of 3800 ng/mL (D6 clone) and 3900 ng/mL (W2 clone), while the lignans 1a-1d, 2a and 3 were inactive. In order to compare the effect on the parasites with toxicity to mammalian cells, the cytotoxic activity of the isolated compounds were evaluated against the Vero cells, showing that all evaluated tetrahydrofuran lignans exhibited no cytotoxicity at the maximum dose tested.