Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite

Autor(es):Mostrar menos -

Mafud, Ana C. ^[1] ; Silva, Marcos P. N. ^[2] ; Monteiro, Daniela C. ^[2] ; Oliveira, Maria F. ^[2] ; Resende, Joao G. ^[2] ; Coelho, Mayara L. ^[3] ; de Sousa, Damiao P. ^[4] ; Mendonca, Ronaldo Z. ^{[5, 2]} ; Pinto, Pedro L. S. ^[6] ; Freitas, Rivelilson M. ^[3] ; Mascarenhas, Yvonne P. ^[1] ; de Moraes, Josue ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[2] Univ Guarulhos, Nucl Pesquisa Doencas Negligenciadas, Guarulhos, SP - Brazil

^[3] Univ Fed Piaui, Rede Nordeste Biotecnol, Programa Posgrad Biotecnol, Teresina, PI - Brazil

^[4] Univ Fed Paraiba, Dept Ciencias Farmaceut, BR-58059900 Joao Pessoa, Paraiba - Brazil

^[5] Inst Butantan, Lab Parasitol, Sao Paulo, SP - Brazil

^[6] Adolfo Lutz Inst, Nucl Enteroparasitas, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Chemico-Biological Interactions; v. 244, p. 129-139, JAN 25 2016.
• Citações Web of Science: 16

Resumo

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 mu M) 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 14/02282-6 - Estudo da relação estrutura-atividade de alcalóides derivados da Pilocarpus microphyllus (Rutaceae) com ação contra Schistosoma mansoni
• Beneficiário: Ana Carolina Mafud
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 00/11624-5 - Embriologia de Gastropoda: análise em microscopia de varredura laser confocal
• Beneficiário: Toshie Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários