4-Nerolidylcatechol and its synthetic analogues: Antioxidant activity and toxicity evaluation

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• 作者：Carla Rosane Mendanha da Cunha^a ; Sebastiã ; o Antô ; nio Mendanha Neto^b ; Claudio Carlos da Silva^c ; Alane Pereira Cortez^a ; Marcelo do Nascimento Gomes^e ; Fabiula Ines Martins^e ; Antô ; nio Alonso^b ; Kê ; nnia Rocha Rezende^d ; Ricardo Menegatti^e ; Mariana Torquato Quezado de Magalhã ; es^f ; Marize Campos Valadares^a ; ^{marizecv@farmacia.ufg.br}
• 关键词：4-Nerolidylcatechol ; Drug design ; Antioxidant activity ; Toxicity ; Safety profile
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：62
• 期：Complete
• 页码：371-378
• 全文大小：713 K

文摘

4-Nerolidylcatechol (1) is a secondary metabolite of plants and is described as a promising anti-inflammatory, antimalarial, antiulcerogenic, analgesic and cytotoxic compound possibly due to its antioxidant profile. In this study, we evaluated the pharmacologic activity and the antioxidant and toxicological profiles of compound (1) and its synthetic analogues (2-6). The synthetic analogues were designed from the lead compound, (1), using a molecular-simplification strategy. Compound 5 showed, by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ¦Â-carotene systems, similar antioxidant activity when compared to compound (1). The oxidative stress in erythrocyte membrane demonstrated the highly protective effect of compounds (4), (5) and (6) and high antioxidant/pro-oxidant activity in relation to the concentrations of compounds (1) and (3). Compounds (2), (4), (5) and (6) were haemobiocompatible. All compounds (1-6) showed cytotoxic effects in 3T3 cells, but compounds (2) and (6) were highly cytotoxic in this lineage when compared to compound (1). Compound (5) had a lower myelosuppressive effect in haematopoietic progenitor cells compared to (1). Both compounds, (1) and (5), showed low genotoxic effects in?vitro, on human lymphocyte cells. In addition, these compounds also showed low-toxicity in?vivo as defined a LD₅₀?>?2000?mg/kg. In this assay, we did not observe death in the animals exposed to treatment with (1) and (5) compound. In conclusion, the structural design of the analogues as validated once compound (5) was found to have an antioxidant profile that was as potent as the lead compound (1). In addition, considering the safety profile, these compounds are promising as preventive and/or therapeutic agents against oxidative damage.