title: Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite.
abstract: 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.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Mafud
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil.
authors.forename: Marcos P N
authors.initials: MP
authors.lastname: Silva
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Monteiro
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Oliveira
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil.
authors.forename: João G
authors.initials: JG
authors.lastname: Resende
authors.affiliation: Programa de Pós-graduação em Biotecnologia, Rede Nordeste de Biotecnologia, Universidade Federal do Piauí, Teresina, PI, Brazil.
authors.forename: Mayara L
authors.initials: ML
authors.lastname: Coelho
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors.forename: Damião P
authors.initials: DP
authors.lastname: de Sousa
authors.affiliation: Laboratório de Parasitologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Ronaldo Z
authors.initials: RZ
authors.lastname: Mendonça
authors.affiliation: Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Pedro L S
authors.initials: PL
authors.lastname: Pinto
authors.affiliation: Programa de Pós-graduação em Biotecnologia, Rede Nordeste de Biotecnologia, Universidade Federal do Piauí, Teresina, PI, Brazil.
authors.forename: Rivelilson M
authors.initials: RM
authors.lastname: Freitas
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Yvonne P
authors.initials: YP
authors.lastname: Mascarenhas
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos, SP, Brazil. Electronic address: josuem@usp.br.
authors.forename: Josué
authors.initials: J
authors.lastname: de Moraes
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D012550:Schistosoma mansoni / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000871:Anthelmintics; D013729:Terpenes
keywords: 3,7-Dimethyl-1-octanol; Antischistosomal compound; Dihydrocitronellol; Schistosoma; Schistosomiasis; Terpene