Subject(s)
Antigens, Protozoan/blood , Blood Donors , DNA, Protozoan/blood , Leishmania infantum/genetics , Leishmaniasis, Visceral/epidemiology , Animals , Antigens, Protozoan/immunology , Asymptomatic Diseases , Brazil/epidemiology , DNA, Protozoan/genetics , Enzyme-Linked Immunosorbent Assay , Humans , Insect Vectors/parasitology , Leishmania infantum/isolation & purification , Leishmaniasis, Visceral/blood , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/transmission , Polymerase Chain Reaction , Prevalence , Psychodidae/parasitologyABSTRACT
The use of natural products has a long tradition in medicine, and they have proven to be an important source of lead compounds in the development of new drugs. Among the natural compounds, terpenoids present broad-spectrum activity against infective agents such as viruses, bacteria, fungi, protozoan and helminth parasites. In this study, we report a biological screening of 38 chemically characterized terpenes from different classes, which have a hydroxyl group connected by hydrophobic chain or an acceptor site, against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. In vitro bioassays revealed that 3,7-dimethyl-1-octanol (dihydrocitronellol) (10) was the most active terpene (IC50 values of 13-52 µM) and, thus, we investigated its antischistosomal activity in greater detail. Confocal laser scanning microscopy revealed that compound 10 induced severe tegumental damage in adult schistosomes and a correlation between viability and tegumental changes was observed. Furthermore, we compared all the inactive compounds with dihydrocitronellol structurally by using shape and charge modeling. Lipophilicity (miLogP) and other molecular properties (e.g. molecular polar surface area, molecular electrostatic potential) were also calculated. From the 38 terpenes studied, compound 10 is the one with the greatest flexibility, with a sufficient apolar region by which it may interact in a hydrophobic active site. In conclusion, the integration of biological and chemical analysis indicates the potential of the terpene dihydrocitronellol as an antiparasitic agent.
Subject(s)
Anthelmintics/chemistry , Anthelmintics/pharmacology , Schistosoma mansoni/drug effects , Terpenes/chemistry , Terpenes/pharmacology , Animals , Cricetinae , Dose-Response Relationship, Drug , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity RelationshipABSTRACT
Garcinielliptone FC (GFC) is a natural prenylated benzophenone found in the seeds of Platonia insignis Mart. (Clusiaceae), a native Brazilian plant. It has been chemically characterized and it is known that GFC has several biological activities such as antioxidant and vasorelaxant properties. In this study, we report the in vitro effect of GFC against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. The anti-S. mansoni activity and cytotoxicity toward mammalian cells were determined for the compound. GFC⩾6.25 µM showed antischistosomal activity and confocal laser scanning microscopy analysis demonstrated several morphological alterations on the tegument of worms, and a correlation between viability and tegumental damage was observed. In addition, at sub-lethal concentrations of GFC (⩽3.125 µM), the number of S. mansoni eggs was reduced. More importantly, GFC exhibited no activity toward mammalian cells and, therefore, there is an appreciable selectivity of this compound against the helminths. In conclusion, these findings indicate the potential of GFC as an antiparasitic agent.
