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 IC50 values ranging from 7.1 to 12.1 μM, comparable
to the positive control (BAY 11-7082, IC50 = 9.7 μM).
Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 μM, being more active than
the positive control (l-NMMA, IC50 = 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 [(5S)-waltherione M, IC50 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 disorders.
