Ortho-nitrobenzyl derivatives as potential anti-schistosomal agents
| Autor: | Brian M. Suzuki, Fábio Vieira dos Santos, Conor R. Caffrey, Glaécia Aparecida do Nascimento Pereira, Marcela Silva Lopes, Renata Barbosa de Oliveira, Alexandra Christina Probst, Júlia Teixeira de Oliveira, Kimberly Brito Tecchio, Rafaela Salgado Ferreira |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Chemistry lcsh:RS1-441 Human cell line Cathepsin B1 biology.organism_classification Cysteine protease In vitro lcsh:Pharmacy and materia medica 03 medical and health sciences 030104 developmental biology Biochemistry Schistosoma mansoni/ anti-schistosomal activity Mutagenicity Nitro-aromatic Electrophile parasitic diseases Parasite hosting Schistosoma mansoni |
| Zdroj: | Brazilian Journal of Pharmaceutical Sciences; Vol. 54 No. 2 (2018); e17376 Brazilian Journal of Pharmaceutical Sciences; Vol. 54 Núm. 2 (2018); e17376 Brazilian Journal of Pharmaceutical Sciences; v. 54 n. 2 (2018); e17376 Brazilian Journal of Pharmaceutical Sciences Universidade de São Paulo (USP) instacron:USP Brazilian Journal of Pharmaceutical Sciences, Vol 54, Iss 2 (2018) |
| ISSN: | 2175-9790 1984-8250 |
| Popis: | In the search for new anti-schistosomal agents, a series of fifteen ortho-nitrobenzyl derivatives was assayed in vitro against both the schistosomulum (somule) and adult forms of Schistosoma mansoni. Compounds 8 and 12 showed significant activity against somules at low micromolar concentrations, but none was active against adults. The SAR demonstrated that the compounds most active against the parasite were mutagenic to the human cell line RKO-AS45-1 only at concentrations 10- to 40-fold higher than the worm-killing dose. Given their electrophilicity, compounds were also screened as inhibitors of the S. mansoni cysteine protease (cathepsin B1) in vitro. Amides 5 and 15 exhibited a modest inhibition activity with values of 55.7 and 50.6 % at 100 µM, respectively. The nitrobenzyl compounds evaluated in this work can be regarded as hits in the search for more active and safe anti-schistosomal agents. |
| Databáze: | OpenAIRE |
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