da Silva Saul Vislei Simões, Barboza Orlando Maia, Souza Jéssica Teles, Soares Érica Novaes, Dos Santos Cleonice Creusa, Pacheco Luciano Vasconcellos, Santos Ivanilson Pimenta, Magalhães Tatiana Barbosa Dos Santos, Soares Milena Botelho Pereira, Guimarães Elisalva Teixeira, Meira Cássio Santana, Costa Silvia Lima, da Silva Victor Diógenes Amaral, de Santana Lourenço Luís Botelho, de Freitas Santos Júnior Aníbal
Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil.
Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil.
Molecules. 2021 Nov 17;26(22):6923. doi: 10.3390/molecules26226923.
Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, H and C NMR spectra. The antioxidant potential was evaluated against the radical ABTS. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production ( < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.
槲皮素（Q）是一种具有生物活性的生物类黄酮；然而，其在水中的溶解度低、广泛的酶促代谢以及生物利用度降低限制了其生物药理学应用。本研究的目的是通过乙酰化对Q进行结构修饰，从而获得槲皮素五乙酸酯（Q5）类似物，以研究其在细胞培养中的生物活性（抗氧化、抗利什曼原虫、抗炎和细胞毒性活性）。通过傅里叶变换红外光谱（FTIR）、氢核磁共振（H NMR）和碳核磁共振（C NMR）光谱对Q5进行了表征。针对ABTS自由基评估了其抗氧化潜力。通过测量BALB/c小鼠腹腔巨噬细胞中促炎细胞因子肿瘤坏死因子（TNF）和一氧化氮（NO）的产生来评估其抗炎潜力。使用阿拉玛蓝法对癌细胞HepG2（人肝癌细胞）、HL-60（早幼粒细胞白血病细胞）和MCR-5（健康人肺成纤维细胞）进行细胞毒性测试，并使用MTT法对C6细胞培养物（大鼠胶质瘤细胞）进行测试。Q和Q5的抗氧化活性分别为29%和18%，这是由于羟基被乙酰基取代所致。Q和Q5均呈现出浓度依赖性地降低NO和TNF的产生（P<0.05）；与地塞米松（20μM）相比，Q和Q5在浓度>40μM时表现出更高的活性。对于HL-60细胞系，与健康细胞系MRC-5（IC>80μM）相比，Q5表现出选择性，可诱导癌细胞死亡。最后，验证了Q5的细胞毒性优势（IC=11μM），其在50μM作用24小时时，可诱导C6胶质瘤细胞形态发生变化，特征为细胞呈圆形（文献中尚未报道）。类似物Q5具有潜在的生物学效应，有望针对其他细胞培养物，特别是神经细胞培养物进行进一步研究。
