Harperoids A-F, Complex Polyprenylated Acylphloroglucinols from Harrisonia perforata that Reverse Multidrug...

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Phloroglucinol derivatives (PPAPs) are known for diverse biological activities.
• Harrisonia perforata is a plant species with potential medicinal applications.

Purpose of the Study:

• To isolate and characterize novel PPAPs from Harrisonia perforata.
• To investigate the anticancer adjuvant potential of isolated compounds.

Main Methods:

• LC/MS-MS-based feature-based molecular networking (FBMN) for compound isolation.
• Comprehensive spectroscopic analysis (NMR, MS) for structure elucidation.
• In vitro cytotoxicity assays and drug-drug interaction studies.
• Molecular docking simulations to understand binding mechanisms.

Main Results:

• Six new PPAPs (1-6) with an acetyl substituent were identified.
• Compound 1 exhibited a unique 5/5/6/5 ring architecture.
• Compounds 5 and 6 featured a benzofuran core and a geranyl-derived cyclohexanol unit.
• Compound 3 showed no cytotoxicity but potentiated paclitaxel activity by 42.8-fold against HCT-15 cells.
• Compound 3 inhibited ABCB1 and ABCG2 transporter function without altering their expression.
• Molecular docking confirmed stable binding of compound 3 to ABCB1 and ABCG2.

Conclusions:

• Novel PPAPs were discovered from Harrisonia perforata.
• Compound 3 demonstrates potential as an anticancer adjuvant by inhibiting drug efflux transporters.
• Further investigation into compound 3's therapeutic applications is warranted.