Structural characterization, antiproliferative and anti-inflammatory activities of alkaloids from the roots of Zanthoxylum austrosinense

• Published in: Bioorganic chemistry 2020-09, Vol.102, p.104101, Article 104101
• Main Authors: Fu, Yan-Hui, Guo, Jia-Ming, Xie, Yu-Tong, Hua, Jing, Dai, Ying-Ying, Zhang, Wei, Lin, Tian-Ci, Liu, Yan-Ping
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory effects; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Antiproliferative activities; Carbazole alkaloids; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Mice; Molecular Structure; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Plant Roots - chemistry; RAW 264.7 Cells; Rutaceae; Structure-Activity Relationship; Zanthoaustrones; Zanthoxylum - chemistry; Zanthoxylum austrosinense
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104101

[Display omitted] •Three new carbazole alkaloids were isolated and characterized from Zanthoxylum austrosinense.•The antiproliferative and anti-inflammatory activities of all isolated alkaloids were tested in vitro.•Alkaloids 1–12 showed remarkable antiproliferative activities equivalent to that of cisplatin.•Alkaloids 1–12 exhibited significant anti-inflammatory effects comparable with that of hydrocortisone. Three new carbazole alkaloids, zanthoaustrones A–C (1–3), as well as nine known compounds 4–12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1–12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1–12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC50 values displaying IC50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents.