Liu Feifei, O'Donnell Timothy J, Park Eun-Jung, Kovacs Sasha, Nakamura Kenzo, Dave Asim, Luo Yuheng, Sun Rui, Wall Marisa, Wongwiwatthananukit Supakit, Silva Dane Kaohelani, Williams Philip G, Pezzuto John M, Chang Leng Chee
School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, People's Republic of China.
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, Hawaii 96720, United States.
J Nat Prod. 2023 Feb 24;86(2):276-289. doi: 10.1021/acs.jnatprod.2c00861. Epub 2023 Feb 6.
Sixteen new quinoline alkaloids (-, , , , -, , and ) and 10 known analogs (, , , , -, and -), along with three known cyclopeptide alkaloids (-), were isolated from the roots of . The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds , , -, , , and reduced TNF-α-induced NF-κB activity with IC values ranging from 7.1 to 12.1 μM, comparable to the positive control (BAY 11-7082, IC = 9.7 μM). Compounds , , , and showed significant NO-inhibitory activity with IC values ranging from 11.0 to 12.8 μM, being more active than the positive control (l-NMMA, IC = 22.7 μM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by [(5)-waltherione M, IC 11.7 ± 0.8 μM] correlated with inhibition of iNOS mRNA expression. The biological potential of metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.
从[植物名称]的根中分离出16种新的喹啉生物碱（-、、、、-、、和）和10种已知类似物（、、、、-和-），以及3种已知的环肽生物碱（-）。通过详细的核磁共振（NMR）、圆二色性（CD）并借助计算辅助以及质谱数据解析，阐明了新化合物的结构。基于细胞培养模型，通过抑制脂多糖（LPS）诱导的一氧化氮（NO）生成以及肿瘤坏死因子-α（TNF-α）诱导的核因子κB（NF-κB）活性，评估了分离物的抗炎潜力。在不抑制细胞生长的情况下，化合物、、-、、、和降低了TNF-α诱导的NF-κB活性，IC值范围为7.1至12.1μM，与阳性对照（BAY 11-7082，IC = 9.7μM）相当。化合物、、和表现出显著的NO抑制活性，IC值范围为11.0至12.8μM，比阳性对照（L-NMMA，IC = 22.7μM）更具活性。构效关系表明，C-8取代对NO抑制活性有显著影响。[化合物名称] [（5）-waltherione M，IC 11.7±0.8μM]对脂多糖诱导的一氧化氮合酶（iNOS）的抑制与iNOS mRNA表达的抑制相关。该植物代谢产物的生物学潜力支持了这种植物在治疗炎症相关疾病方面的传统用途。
