Lignan constituents of Tilia amurensis and their biological evaluation on antitumor and anti-inflammatory activities

In the recent decade, numerous lignan derivatives isolated from plants have been proven to have the potential as an anti-cancer substance. On the search for anti-cancer compounds from Korean medicinal plants, the methanolic extract from the trunk of Tilia amurensis Rupr. (Tiliaceae) was found to have significant cytotoxicity against A549 (lung carcinoma), SK-OV-3 (ovary malignant ascites), SK-MEL-2 (skin melanoma), and HCT-15 (colon adenocarcinoma) in our screening test. Hence, a bioassay-guided fractionation and chemical investigation of the methanolic extract resulted in the isolation and identification of 10 lignan derivatives (1-10) including two new lignan glycosides named tiliamurosides A (1) and B (2). The structures of these new compounds were determined by spectroscopic methods, namely 1D and 2D nuclear magnetic resonance (NMR) techniques, high resolution mass spectrometry (HRMS), circular dichroism (CD) data, and chemical methods. Tiliamuroside B (2) and schizandriside (3) showed significant cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with inhibitory concentration (IC50) values of 3.26-8.89 μM. Moreover, (−)-syringaresinol (8) and (−)-pinoresinol 4-O-β-d-glucopyranoside (10) significantly inhibited nitric oxide (NO) production in murine microglia BV-2 with IC50 values of 15.05 and 34.35 μM, respectively.

Graphical abstractDownload full-size imageHighlights► This study deals with the isolation and biological study of 10 lignan derivatives from Tilia amurensis. ► The MeOH extract from the trunk of T. amurensis showed significant cytotoxicity against four tumor cells. ► We attempted to investigate the antitumor constituents of T. amurensis. ► Using the bioactivity-guided isolation techniques, 10 lignans including two new lignan glycosides were isolated. ► We confirmed the anticancer and anti-inflammatory effects of the lignan derivatives.