Abstract

Chalcones are aromatic compounds found in plants or obtained by synthetic methods. These compounds and their derivatives have been proven to be responsible for a variety of pharmacological properties, including anti-inflammatory and anticancer activities. A second interesting class of compound are coumarins which comprises a large class of molecules derived from phenolic compounds found mainly in plants, exhibiting multiple biological activities such as antioxidant and anti-tumoral properties. Due to the relevance of these compounds, this study aimed to investigate the genotoxic/antigenotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one (2HMC) and the coumarin–chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl)acryloyl-2H-cromen-2-one] (4-MET) using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To assess the mutagenic and recombinogenic activities, larvae derived from standard and high bioactivation crosses were treated with different concentrations of 2HMC (10, 50, 100 and 400 µg/mL) or 4-MET (5, 50, 100 and 400 µg/mL) for 48 h. Dimethylsulfoxide (DMSO, 0.5%) was the negative control group. The anti-recombinogenic and antimutagenic activities were assessed using larvae from both crosses co-treated with the same concentrations of 2HMC or 4-MET and mitomycin C (MMC, 0.05 mM). SMART revealed no mutagenic or recombinogenic effects since no significant increase of any category of mutant spots was observed (p > 0.05). However, both compounds reduced the frequency of all spots induced by MMC showing antimutagenic and anti-recombinogenic activities in D. melanogaster cells from both crosses. We suggest that the antimutagenic and anti-recombinogenic activities observed in our study may have been a result of the antioxidant activity of 2HMC and 4-MET.

摘要

查耳酮是在植物中发现或通过合成方法获得的芳香族化合物。这些化合物及其衍生物已被证明具有多种药理特性，包括抗炎和抗癌活性。第二类有趣的化合物是香豆素，它包含一大类来源于酚类化合物的分子，这些酚类化合物主要存在于植物中，具有多种生物活性，例如抗氧化和抗肿瘤特性。由于这些化合物的相关性，本研究旨在调查查耳酮 (E)-1-(2-羟基苯基)-3-(4-甲基苯基)-prop-2-en-1-one 的基因毒性/抗原毒性作用(2HMC) 和香豆素-查耳酮杂化物 [7-methoxy-3-( E )-3-(3,4,5-trimethoxyphenyl)acryloyl-2 H-cromen-2-one] (4-MET) 在黑腹果蝇中使用体细胞突变和重组测试 (SMART) 。为了评估诱变和重组活性，来自标准和高生物活性杂交的幼虫用不同浓度的 2HMC（10、50、100 和 400 µg/mL）或 4-MET（5、50、100 和 400 µg/mL）处理) 48 小时。二甲基亚砜（DMSO，0.5%）为阴性对照组。使用来自与相同浓度的 2HMC 或 4-MET 和丝裂霉素 C (MMC, 0.05 mM) 共同处理的两个杂交的幼虫评估抗重组和抗诱变活性。SMART 显示没有诱变或重组效应，因为没有观察到任何类别的突变点显着增加（p > 0.05)。然而，这两种化合物都降低了 MMC 诱导的所有斑点的频率，这些斑点在来自两个杂交的黑腹果蝇细胞中显示出抗诱变和抗重组活性。我们认为，在我们的研究中观察到的抗诱变和抗重组活性可能是 2HMC 和 4-MET 的抗氧化活性的结果。