Complex Chalcone Scaffolds from Mallotus philippinensis Fruits as Potential iNOS Inhibitors

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Phytochemistry

Background:

• Chalcones are vital structural motifs in natural and synthetic compounds with significant biological activities.
• Mallotus philippinensis is a known source of diverse chalcones, including rare complex dimeric forms.
• Only five complex dimeric chalcones had been previously identified from this species.

Purpose of the Study:

• To discover and characterize novel complex dimeric chalcones from Mallotus philippinensis.
• To investigate the anti-inflammatory potential of the isolated compounds.

Main Methods:

• Isolation and structural elucidation of six new compounds, runachalcones A-F, using NMR spectroscopy and HR-ESIMS.
• Determination of absolute configurations via J-based analysis, ROESY, and quantum mechanical ECD calculations.
• In vitro anti-inflammatory assay using RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS).

Main Results:

• Six novel complex dimeric chalcones, designated runachalcones A-F, were successfully isolated and identified.
• The planar structures and absolute configurations of the new compounds were rigorously determined.
• Runachalcone F significantly suppressed LPS-induced inducible nitric oxide synthase (iNOS) protein expression and nitric oxide production.

Conclusions:

• The discovery of runachalcones A-F expands the known chemical diversity of dimeric chalcones.
• Mallotus philippinensis fruits represent an underexplored source of complex natural products.
• Runachalcone F exhibits promising anti-inflammatory activity, warranting further investigation.