Maioli Margherita, Basoli Valentina, Carta Paola, Fabbri Davide, Dettori Maria Antonietta, Cruciani Sara, Serra Pier Andrea, Delogu Giovanna
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Bologna, Italy.
PLoS One. 2018 Feb 7;13(2):e0192178. doi: 10.1371/journal.pone.0192178. eCollection 2018.
The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to conventional chemotherapies. Thus, the search for novel therapeutic leads is of global interest. Herein, a small set of derivatives of magnolol 1 and honokiol 2, the main components of Magnolia grandiflora and Magnolia obovata, were evaluated in in vitro assay using tumoral hepatocytes. The pro-drug approach was applied as versatile strategy to the improve bioactivity of the compounds by careful transformation of the hydroxyl groups of magnolol 1 and honokiol 2 in suitable ester derivatives. Compounds 10 and 11 resulted to be more potent than the parental honokiol 2 at concentration down to 1 μM with complete viability of treated fibroblast cells up to concentrations of 80 μM. The combination of a butyrate ester and a bare phenol-OH group in the honokiol structure seemed to play a significant role in the antiproliferative activity identifying an interesting pharmacological clue against hepatocellular carcinoma.
肝细胞癌是最常见的恶性肿瘤之一，因其进展迅速且对传统化疗具有高度抗性，死亡率很高。因此，寻找新的治疗方法备受全球关注。在此，对厚朴酚1和和厚朴酚2（厚朴和凹叶厚朴的主要成分）的一小部分衍生物，使用肿瘤肝细胞进行了体外试验评估。前药方法作为一种通用策略，通过将厚朴酚1和和厚朴酚2的羟基小心转化为合适的酯衍生物，来提高化合物的生物活性。化合物10和11在浓度低至1 μM时比亲本和厚朴酚2更有效，在高达80 μM的浓度下，处理过的成纤维细胞仍具有完全活力。和厚朴酚结构中丁酸酯和裸露酚羟基的组合似乎在抗增殖活性中起着重要作用，为肝细胞癌提供了一个有趣的药理学线索。
