Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica

作者：Feifei Liu, Timothy J. O’Donnell, Eun‐Jung Park, Sasha Kovacs, Kenzo Nakamura, Asim Dave, Yuheng Luo, Rui Sun, Marisa M. Wall, Supakit Wongwiwatthananukit, Dane Kaohelani Silva, Philip G. Williams, John M. Pezzuto, Leng Chee Chang · 发表于：Journal of Natural Products · 年份：2023 · DOI：10.1021/acs.jnatprod.2c00861 · 被引用次数：12 · 研究领域：Ziziphus Jujuba Studies and Applications、Natural product bioactivities and synthesis、Biological Activity of Diterpenoids and Biflavonoids

Sixteen new quinoline alkaloids ( 1a – 7, 8a, 9, 10, 13 – 15, 17, and 21 ) and 10 known analogs ( 8b, 11, 12, 16, 18 – 20, and 22 – 24 ), along with three known cyclopeptide alkaloids ( 25 – 27 ), were isolated from the roots of Waltheria indica . 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 6, 8a, 9 – 11, 13, 21, and 24 reduced TNF-α-induced NF-κB activity with IC 50 values ranging from 7.1 to 12.1 μM, comparable to the positive control (BAY 11-7082, IC 50 = 9.7 μM). Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC 50 values ranging from 11.0 to 12.8 μM, being more active than the positive control ( l -NMMA, IC 50 = 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 8b [(5 S )-waltherione M, IC 50 11.7 ± 0.8 μM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related diso...