Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of <i>Linum austriacum</i> and <i>Linum perenne</i>.
Tóth G, Horváti K, Kraszni M, Ausbüttel T, Pályi B, Kis Z, Mucsi Z, Kovács GM, Bősze S, Boldizsár I.
Diphyllin (<b>1</b>) and justicidin B (<b>2</b>) are arylnaphthalene lignans with antiviral and antiproliferative effects. Compound <b>1</b> is also known as an effective inhibitor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the <i>in vitro</i> antiviral and cytotoxic potency of both lignans in SARS-CoV-2 -infected cells and various cancer cell lines, respectively, <b>1</b> and <b>2</b> were isolated from the underground organs of <i>Linum austriacum</i> and <i>Linum perenne</i>. Two previously undescribed arylnaphthalene lignans, denominated linadiacin A and B (<b>3</b> and <b>4</b>), were also isolated and identified. In acidic media, <b>3</b> was converted by a two-step reaction into <b>2</b> via the intermediate <b>4</b>. Optimum acid treatment conditions were determined to isolate lignans by one-step preparative high-performance liquid chromatography (HPLC). The results of the conversion, HPLC-tandem mass spectrometry, nuclear magnetic resonance spectroscopy, and molecular modeling studies allowed complete structure analysis. Compounds <b>1</b> and <b>2</b> were the most effective against SARS-CoV-2 with a 3-log reduction in the viral copy number at a 12.5 μM concentration. Ten human cancer cell lines showed sensitivity to at least one of the isolated lignans.