In Vitro Synergistic Interaction Between Amide Piplartine and Antimicrobial Peptide Dermaseptin Against Schistosoma mansoni Schistosomula and Adult Worms

Autor(es)

de Moraes, J. ^{[1, 2]} ; Keiser, J. ^{[3, 4]} ; Ingram, K. ^{[3, 4]} ; Nascimento, C. ^[1] ; Yamaguchi, L. F. ^[5] ; Bittencourt, C. R. ^[6] ; Bemquerer, M. P. ^[7] ; Leite, J. R. ^[6] ; Kato, M. J. ^[5] ; Nakano, E. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Parasitol Lab, BR-05503900 Sao Paulo - Brazil

^[2] Secretaria Saude Cidade Sao Paulo, SUVIS Casa Verde, Sao Paulo, SP - Brazil

^[3] Swiss Trop & Publ Hlth Inst, Dept Med Parasitol & Infect Biol, CH-4002 Basel - Switzerland

^[4] Univ Basel, Basel - Switzerland

^[5] Univ Sao Paulo, Inst Quim, Sao Paulo - Brazil

^[6] Univ Fed Piaui, BIOTEC, Nucleo Pesquisa Biodiversidade & Biotecnol, Parnaiba, PI - Brazil

^[7] EMBRAPA Recursos Genet & Biotecnol, Brasilia, DF - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Current Medicinal Chemistry; v. 20, n. 2, p. 301-309, JAN 2013.
• Citações Web of Science: 23

Resumo

Schistosomiasis is one of the world's major public health problems, and praziquantel is the only available drug to treat this notable neglected disease. Drug combinations have been considered an important strategy for treatment of infectious diseases, which might enhance therapeutic efficacy and delaying resistance. In this study, we have examined the in vitro activities of the amide piplartine and the antimicrobial peptide dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including 3-hour-old and 7-day-old schistosomula and 49-day-old adult schistosomes as well as on egg output by adult worms. We calculated the median lethal concentrations (LC50) of 7.87 and 17.99 mu M on 49-day-old adults, 11.02 and 71.58 mu M on 7-day-old schistosomula, and 70.87 and 98.42 mu M on 3-hour-old schistosomula for piplartine and dermaseptin, respectively. Most Piplartine/dermaseptin combinations showed synergistic effect, with combination index (CI) values less than 0.9 when S. mansoni adults or schistosomula were simultaneously incubated with both drugs in vitro; synergy between these two compounds was also indicated using isobolograms. Additionally, we observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy. Furthermore, egg laying of surviving worms was considerably more reduced when exposed to the piplartine/dermaseptin combinations than each drug alone, and this inhibition was irreversible. This is the first report on the synergistic effect between piplartine and dermaseptin against S. mansoni and opens the route to further studies (e. g. in vivo) to characterize this combination in greater detail. (AU)

• Processo FAPESP: 06/56216-8 - Effect of plant extracts on Biomphalaria glabrata, vector of schistosomiasis, and on Schistosoma mansoni
• Beneficiário: Toshie Kawano
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 00/11624-5 - Embriologia de Gastropoda: análise em microscopia de varredura laser confocal
• Beneficiário: Toshie Kawano
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários