Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India.
Department of Animal Science, Kazi Nazrul University, Asansol 713340, West Bengal, India.
Eur J Pharm Sci. 2019 Jun 15;134:102-115. doi: 10.1016/j.ejps.2019.04.016. Epub 2019 Apr 16.
A series of aryl 7-chloroquinolinyl hydrazone derivatives (3a-u) have been synthesized in 55-76% yield using simple reaction condition. The synthesized compounds were evaluated for their anti-inflammatory activities based on their ability to inhibit pro-inflammatory cytokine secretion from the macrophages after stimulation with lipopolysaccharide (LPS). Three compounds appeared as promising anti-inflammatory agents. The mechanism of inflammatory activity of the potent compound 3e was further investigated using a series of biochemical, molecular and microscopic techniques. Further structure activity relationship (SAR) study was carried out to validate the anti-inflammatory activities of the active compounds. Our experimental data revealed that the active moiety i.e. compound 3e majorly causes inhibition of TLR4 signaling pathway and this appears to be the novel functional attribute of this compound.
一系列芳基 7-氯喹啉基腙衍生物（3a-u）已在简单的反应条件下以 55-76%的收率合成。根据抑制脂多糖（LPS）刺激后巨噬细胞中促炎细胞因子分泌的能力，对合成的化合物进行了抗炎活性评价。三种化合物表现出有希望的抗炎作用。进一步使用一系列生化、分子和显微镜技术研究了强效化合物 3e 的炎症活性机制。进行了进一步的构效关系（SAR）研究以验证活性化合物的抗炎活性。我们的实验数据表明，活性部分即化合物 3e 主要导致 TLR4 信号通路的抑制，这似乎是该化合物的新功能属性。
