Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy.
Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2/3, 28100 Novara, Italy.
J Nat Prod. 2020 Jun 26;83(6):1740-1750. doi: 10.1021/acs.jnatprod.9b00685. Epub 2020 Jun 4.
Bitter taste receptors (hTAS2R) are expressed ectopically in various tissues, raising the possibility of a pharmacological exploitation. This seems of particular relevance in airways, since hTAS2Rs are involved in the protection of the aerial tissues from infections and in bronchodilation. The bis-guaianolide absinthin (), one of the most bitter compounds known, targets the hTAS2R46 bitter receptor. Absinthin (), an unstable compound, readily turns into anabsinthin () with substantial retention of the bitter properties, and this compound was used as a starting material to explore the chemical space around the bis-guaianolide bitter pharmacophore. Capitalizing on the chemoselective opening of the allylic lactone ring, the esters and , and the -azide were prepared and assayed on human bronchoepithelial (BEAS-2B) cells expressing hTAS2R46. Anti-inflammatory activity was evaluated by measuring the expression of MUC5AC, iNOS, and cytokines, as well as the production of superoxide anion, qualifying the methyl ester as the best candidate for additional studies.
苦味受体（hTAS2R）在各种组织中异位表达，这为药理学的开发提供了可能性。这在气道中似乎特别相关，因为 hTAS2R 参与保护空气组织免受感染和支气管扩张。双古莲醇类苦艾素（）是已知最苦的化合物之一，它的靶点是 hTAS2R46 苦味受体。苦艾素（）是一种不稳定的化合物，很容易转化为苦艾素（），苦味特性基本保留，这种化合物被用作探索双古莲醇类苦味药效基团周围化学空间的起始材料。利用烯丙基内酯环的选择性开环，制备了酯和，并对表达 hTAS2R46 的人支气管上皮（BEAS-2B）细胞进行了检测。通过测量 MUC5AC、iNOS 和细胞因子的表达以及超氧阴离子的产生来评估抗炎活性，将甲酯鉴定为进一步研究的最佳候选物。
