Highly Aromatic Flavan-3-ol Derivatives from Palaeotropical Artocarpus lacucha Buch.-Ham Possess Radical Scavenging and Antiproliferative Properties

Abstract

Phytochemical investigation of leaves and stembark of <i>Artocarpus lacucha</i> collected in Thailand resulted in three yet undescribed isomeric flavan-3-ol derivatives (<b>1</b>-<b>3</b>), the four known compounds gambircatechol (<b>4</b>), (+)-catechin (<b>5</b>), (+)-afzelechin (<b>6</b>) and the stilbene oxyresveratrol (<b>7</b>). Compounds <b>1</b> to <b>3</b> feature 6/6/5/6/5/6 core structures. All structures were deduced by NMR and MS, while density functional theory (DFT) calculations on B3LYP theory level were performed of compounds <b>1</b> to <b>3</b> to support the stereochemistry in positions 2 and 3 in the C-ring. Possible biosynthetic pathways leading to <b>4</b> are discussed. The DPPH assay revealed high radical scavenging activities for <b>1</b> (EC₅₀ = 9.4 ± 1.0 µmol mL^-1), <b>2</b> (12.2 ± 1.1), <b>3</b> (10.0 ± 1.5) and <b>4</b> (19.0 ± 2.6), remarkably lower than ascorbic acid (EC₅₀ = 34.9) and α-tocopherol (EC₅₀ = 48.6). A cytotoxicity assay revealed moderate but consistent antiproliferative properties of <b>1</b> in CH1/PA-1 (ovarian teratocarcinoma) and SW480 (colon carcinoma) cells, with IC₅₀ values of 25 ± 6 and 34 ± 4 µM, respectively, whereas effects in A549 (non-small cell lung cancer) cells were rather negligible. The performed DCFH-DA assay of <b>1</b> in the former cell lines confirmed potent antioxidative effects even in the cellular environment.