Parisi Valentina, Donadio Giuliana, Bellone Maria Laura, Belaabed Soumia, Bader Ammar, Bisio Angela, Iobbi Valeria, Gazzillo Erica, Chini Maria Giovanna, Bifulco Giuseppe, Faraone Immacolata, Vassallo Antonio
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.
Department of Chemistry, Research Unit, Development of Natural Resources, Bioactive Molecules Physicochemical and Biological Analysis, University Brothers Mentouri, Route Ain ElBey, Constantine 25000, Algeria.
Plants (Basel). 2023 Jun 22;12(13):2421. doi: 10.3390/plants12132421.
, a genus consisting of approximately 200 species, predominantly thrives in tropical and subtropical areas. Many of these species have been utilized in ethnopharmacology for diverse medicinal applications. In Saudi Arabia, (Hochst.) Schauer (Lamiaceae) grows wildly, and its slightly viscid leaves are attributed to the production of leaf accession. In this study, we aimed to extract the surface accession from fresh leaves using dichloromethane to evaluate the anticancer potential. The plant exudate yielded two previously unknown labdane diterpenes, Premnaresone A and B, in addition to three already described congeners and four known flavonoids. The isolation process was accomplished using a combination of silica gel column chromatography and semi-preparative HPLC, the structures of which were identified by NMR and HRESIMS analyses and a comparison with the literature data of associated compounds. Furthermore, we employed a density functional theory (DFT)/NMR approach to suggest the relative configuration of different compounds. Consequently, we investigated the possibility of developing new chaperone inhibitors by subjecting diterpenes - to a Surface Plasmon Resonance-screening, based on the knowledge that oridonin, a diterpene, interacts with Heat Shock Protein 70 (Hsp70) 1A in cancer cells. Additionally, we studied the anti-proliferative activity of compounds - on human Jurkat (human T-cell lymphoma) and HeLa (epithelial carcinoma) cell lines, where diterpene 3 exhibited activity in Jurkat cell lines after 48 h, with an IC of 15.21 ± 1.0 µM. Molecular docking and dynamic simulations revealed a robust interaction between compound and Hsp70 key residues.
该属约有200个物种，主要生长在热带和亚热带地区。其中许多物种已被用于民族药理学的各种药用。在沙特阿拉伯，假荆芥（Hochst.）Schauer（唇形科）野生生长，其叶片稍有粘性归因于叶分泌物的产生。在本研究中，我们旨在用二氯甲烷从新鲜叶片中提取表面分泌物，以评估其抗癌潜力。该植物分泌物除了产生三种已描述的同系物和四种已知黄酮类化合物外，还产生了两种以前未知的半日花烷二萜，假荆芥素A和B。分离过程采用硅胶柱色谱和半制备高效液相色谱相结合的方法完成，其结构通过核磁共振和高分辨电喷雾电离质谱分析以及与相关化合物的文献数据比较来确定。此外，我们采用密度泛函理论（DFT）/核磁共振方法来推测不同化合物的相对构型。因此，基于二萜冬凌草甲素与癌细胞中的热休克蛋白70（Hsp70）1A相互作用的知识，我们通过表面等离子体共振筛选研究了开发新型伴侣抑制剂的可能性。此外，我们研究了这些化合物对人Jurkat（人T细胞淋巴瘤）和HeLa（上皮癌）细胞系的抗增殖活性，其中二萜3在48小时后在Jurkat细胞系中表现出活性，IC50为15.21±1.0μM。分子对接和动力学模拟揭示了化合物3与Hsp70关键残基之间的强相互作用。
