Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages
Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages
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DOI：
10.1016/j.bmc.2010.03.020
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发表时间：
2010-04-15
影响因子：
3.5
通讯作者：
Li, Jian-Xin
中科院分区：
文献类型：
--
作者：
Liu, Guo-Biao;Xu, Jian-Liang;Li, Jian-Xin
合成了一系列新的二酚类色素衍生物，并分别采用lps激活小鼠巨噬细胞RAW264.7法和MTT法评价了二酚类色素衍生物对一氧化氮（NO）产生的抑制活性和细胞毒性。其中，（5,7-二羟基-4-氧- 4h -铬-3-基）甲酯（6b、6c、6f、6g和6h）具有较强的抑制活性，IC50值分别为2.20、3.48、0.35、0.80和0.61 μ M。MTT结果表明，在有效浓度下，所有活性化合物均无细胞毒性。根据RT-PCR结果进一步研究了最有效的化合物（6b、6c、6f、6g和6h）的初步机制，发现化合物6f、6g和6h通过抑制iNOS mRNA的表达呈剂量依赖性抑制NO的产生。此外，物理化学参数的计算分析表明，大多数化合物具有类似药物的性质。(C) 2010 Elsevier Ltd.版权所有。
A novel series of diphenolic chromone derivatives were synthesized and their inhibitory activity on nitric oxide (NO) production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, (5,7-dihydroxy-4-oxo-4H-chromen-3-yl) methyl esters (6b, 6c, 6f, 6g, and 6h) showed quite potent inhibitory activities with IC50 values of 2.20, 3.48, 0.35, 0.80, and 0.61 mu M, respectively. The MTT results showed that all of the active compounds exhibited no cytotoxicity at the effective concentrations. The preliminary mechanism of the most potent compounds (6b, 6c, 6f, 6g, and 6h) was further examined based on the RT-PCR results and the compounds 6f, 6g, and 6h inhibited NO production by suppressing the expression of iNOS mRNA in a dose dependent manner. Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug-like properties. (C) 2010 Elsevier Ltd. All rights reserved.