Limonoids Containing a C₁⁻O⁻C₂₉ Moiety: Isolation, Structural Modification, and Antiviral Activity

Area of Science:

• Natural Products Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Xylocarpus granatum, a mangrove plant, is a source of bioactive limonoids.
• Limonoids are known for diverse pharmacological activities, including antiviral properties.

Purpose of the Study:

• To isolate and characterize new limonoids from Thai Xylocarpus granatum seeds.
• To evaluate the antiviral activity of isolated compounds and their derivatives against HIV-1 and IAV.

Main Methods:

• Isolation and structure elucidation using HR-ESIMS and NMR spectroscopy.
• Determination of absolute configuration via single-crystal X-ray diffraction and ECD spectroscopy.
• Chemical modification of granatumin L and in vitro antiviral assays.

Main Results:

• Five new limonoids, thaigranatins A-E (1-5), and known granatumin L (6) were isolated.
• Derivative 8i demonstrated potent HIV-1 inhibition (IC50 = 15.98 μM) with low toxicity (CC50 > 100.0 μM).
• Derivative 10b showed significant IAV inhibition (IC50 = 14.02 μM) with low toxicity (CC50 > 100.0 μM).

Conclusions:

• Thaigranatins A-E are novel limonoids from Xylocarpus granatum.
• Derivative 8i is a promising candidate for HIV-1 treatment.
• Derivative 10b represents a potential therapeutic agent for influenza A virus infections.