دورية أكاديمية
Synthesis and evaluation of the antiparasitic activity of bis-(arylmethylidene) cycloalkanones.
| العنوان: | Synthesis and evaluation of the antiparasitic activity of bis-(arylmethylidene) cycloalkanones. |
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| المؤلفون: | Braga SF; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil., Alves ÉV; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil., Ferreira RS; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil., Fradico JR; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil., Lage PS; Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Duarte MC; Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Ribeiro TG; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil., Júnior PA; Centro de Pesquisas René Rachou, FIOCRUZ, Avenida Augusto de Lima, 1.715, Barro Preto, Belo Horizonte 30.190-002, MG, Brazil., Romanha AJ; Centro de Pesquisas René Rachou, FIOCRUZ, Avenida Augusto de Lima, 1.715, Barro Preto, Belo Horizonte 30.190-002, MG, Brazil., Tonini ML; Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Setor F, Bloco A, Florianópolis 88.040-970, SC, Brazil., Steindel M; Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Setor F, Bloco A, Florianópolis 88.040-970, SC, Brazil., Coelho EF; Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., de Oliveira RB; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte 31.270-901, MG, Brazil. Electronic address: renatabo@farmacia.ufmg.br. |
| المصدر: | European journal of medicinal chemistry [Eur J Med Chem] 2014 Jan; Vol. 71, pp. 282-9. Date of Electronic Publication: 2013 Nov 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| مواضيع طبية MeSH: | Antiprotozoal Agents/*chemistry , Antiprotozoal Agents/*pharmacology , Leishmania mexicana/*drug effects , Trypanosoma cruzi/*drug effects, Animals ; Cell Line ; Chagas Disease/drug therapy ; Fibroblasts/drug effects ; Fibroblasts/parasitology ; Humans ; Leishmaniasis, Cutaneous/drug therapy ; Macrophages/drug effects ; Macrophages/parasitology ; Mice ; Models, Molecular |
| مستخلص: | A series of bis-(arylmethylidene)-cycloalkanones was synthesized by cross-aldol condensation. The activity of the compounds was evaluated against amastigotes forms of Trypanosoma cruzi and promastigotes forms of Leishmania amazonensis. The cytotoxicity of the active compounds on uninfected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their antiparasitic effects. Six compounds displayed trypanocidal activity against amastigotes intracellular forms of T. cruzi with IC₅₀ values ranging from 7.0 to 249 μM. Besides these six compounds, eight other molecules exhibited significant leishmanicidal activity (IC₅₀ values ranging from 0.6 to 110.4 μM). Two compounds can be considered as promising antiparasitic lead molecules because they showed IC₅₀ values in the low-micromolar range (≤1.2 μM) with an adequate SI (≥19.9). To understand the mechanism of action of these compounds, two possible molecular targets were investigated: trypanothione reductase (TR) and cruzain. (Copyright © 2013 Elsevier Masson SAS. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antileishmanial activity; BJGPXDMLZSYWLM-OZNQKUEASA-N; BRBMTEYZYVZFJD-IWGRKNQJSA-N; Bis-(arylmethylidene)-cycloalkanones; CETXDHNPPYXEOF-OZNQKUEASA-N; CTKKGXDAWIAYSA-JSAVKQRWSA-N; CVTOCKKPVXJIJK-HBKJEHTGSA-N; CYVVJSKZRBZHAV-UNZYHPAISA-N; DYLUMQZRSQEPTH-UHFFFAOYSA-N; GPXHIYXWGUYGHF-MXWIWYRXSA-N; IEJNKQYBMJIRJU-MXWIWYRXSA-N; IXIITVGWLWCRQL-IWGRKNQJSA-N; Leishmania amazonensis; MFRNIFJHZVDERH-UHFFFAOYSA-N; MOGZMXKHFUIRHE-RYQLWAFASA-N; OPTXWXOODPUHHD-UHFFFAOYSA-N; QBJZDRXWVFLWLM-AYKLPDECSA-N; SGFZCAFEUGISMF-WXGDAXOSSA-N; Trypanocidal; Trypanosoma cruzi; UKIUACHVRRQMGB-DCIPZJNNSA-N; UMLFTCYAQPPZER-UHFFFAOYSA-N; VJTIKIQJUZWNSW-JOBJLJCHSA-N; WRGGDYGLRCBKGJ-NWILIBCHSA-N; XRJCFZUOXQVWGF-NWILIBCHSA-N; XYPVBKDHERGKJG-UHFFFAOYSA-N; ZXCMCPINSJLVEY-WGDLNXRISA-N |
| المشرفين على المادة: | 0 (Antiprotozoal Agents) |
| تواريخ الأحداث: | Date Created: 20131211 Date Completed: 20140918 Latest Revision: 20140131 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.ejmech.2013.11.011 |
| PMID: | 24321832 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2013.11.011 |