Two Triterpenoids with a Cyclobutane Moiety from Mastic: Structural Elucidation and Biological Evaluation

Area of Science:

• Natural Product Chemistry
• Organic Chemistry
• Pharmacology

Background:

• Mastic (Pistacia lentiscus L.) is a resin with a long history of medicinal use.
• Triterpenoids are a diverse class of natural products with a wide range of biological activities.
• Novel chemical structures with unique biological properties are continuously sought from natural sources.

Purpose of the Study:

• To isolate and characterize novel triterpenoids from mastic.
• To investigate the structural features and potential biological activities of these compounds.
• To explore new therapeutic leads from natural products.

Main Methods:

• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation employing Nuclear Magnetic Resonance (NMR) spectroscopy, ACD/SE, QCC-NMR, and Electronic Circular Dichroism (ECD) analysis.
• In vitro assays to evaluate antiproliferative and anti-inflammatory activities.

Main Results:

• Isolation of two novel triterpenoids, cyclobutastics A (1) and B (2).
• Compound 1 possesses a rare pentacyclic framework with a cyclobutane ring (C-1 to C-11).
• Compound 2 exhibits an unprecedented cyclobutane linkage (C-8 to C-18) and demonstrated significant inhibition of human colorectal adenocarcinoma SW480 and HCT116 cell proliferation (IC50 values 15.2 ± 1.3 and 3.8 ± 0.7 μM, respectively).
• Compound 2 also displayed moderate anti-inflammatory activity (IC50 = 24.7 ± 1.5 μM).

Conclusions:

• The discovery of cyclobutastics A and B expands the known structural diversity of triterpenoids.
• Compound 2 represents a novel structural motif in natural triterpenoids.
• Compound 2 shows promising potential as an anti-cancer and anti-inflammatory agent, warranting further investigation.