Synthesis, characterization, and anti‐inflammatory properties of novel ethyl 3‐benzoyl‐7‐(trifluoromethyl)indolizine‐1‐carboxylate derivatives: In silico and in vitro analysis,Chemical Biology & Drug Design

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Synthesis, characterization, and anti‐inflammatory properties of novel ethyl 3‐benzoyl‐7‐(trifluoromethyl)indolizine‐1‐carboxylate derivatives: In silico and in vitro analysis
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2024-03-27 , DOI: 10.1111/cbdd.14514
Harshada Rambaboo Singh ₁ , Prajjwal Kushwaha ₂ , Reetika Tandon ₂ , Nidhi Srivastava ₂ , Sandeep Chandrashekharappa ₁

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Series of 7‐(Trifluoromethyl) substituted indolizine 4a‐g was synthesized using the one‐pot method. Spectroscopic techniques such as IR, 1H‐NMR, 13C‐NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a‐g compounds were tested for their anti‐inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a‐g selectively targeting COX‐2 enzyme, tumor necrosis factor‐α (TNF‐α) and, interleukin‐6 (IL‐6). The in silico docking studies of 4a‐g showed that these compounds have a higher affinity for COX‐2 enzyme, TNF‐ α, and IL‐6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood–brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX‐2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF‐α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL‐6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti‐inflammatory activities of these novel 7‐(Trifluoromethyl) substituted indolizine derivatives.

中文翻译：

新型 3-苯甲酰基-7-(三氟甲基)中氮茚-1-甲酸乙酯衍生物的合成、表征和抗炎特性：计算机和体外分析

采用一锅法合成了一系列7-(三氟甲基)取代中氮茚4a-g。光谱技术，例如 IR、 1核磁共振氢谱， 13 C-NMR和HRMS用于新合成化合物的结构确认。测试了这些 4a-g 化合物的抗炎活性。在这项研究中，我们鉴定了新型中氮茚衍生物化合物 4a-g，选择性靶向 COX-2 酶、肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6)。 4a-g 的计算机对接研究表明，这些化合物对 COX-2 酶、TNF-α 和 IL-6 具有更高的亲和力。计算机 ADME 谱分析预测这些化合物具有良好的胃肠道和血脑屏障吸收性。体外研究表明，与吲哚美辛相比，化合物 4d 显着降低 COX-2 酶的水平。还发现化合物 4e、4f 和 4a 显着降低 TNF-α 水平，而与吲哚美辛相比，化合物 4f、4g 和 4d 显示 IL-6 水平降低。与吲哚美辛相比，化合物 4a、4d 和 4f 还可降低一氧化氮 (NO) 水平。总体而言，当前的研究表明这些新型 7-（三氟甲基）取代的中氮茚衍生物具有显着的抗炎活性。

更新日期：2024-03-27

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