Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of Linum austriacum and Linum perenne

  • J Nat Prod. 2023 Apr 28;86(4):672-682. doi: 10.1021/acs.jnatprod.2c00580.
Gergő Tóth  1 ,  Kata Horváti  2 ,  Márta Kraszni  1 ,  Tim Ausbüttel  3  4 ,  Bernadett Pályi  5 ,  Zoltán Kis  5 ,  Zoltán Mucsi  6 ,  Gábor M Kovács  4 ,  Szilvia Bősze  5  7 ,  Imre Boldizsár  3  4
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9, Budapest 1092, Hungary.
  • 2. MTA-TTK Lendület "Momentum" Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Magyar Tudósok krt 2, Budapest 1117, Hungary.
  • 3. Department of Pharmacognosy, Semmelweis University, Üllői út 26, Budapest 1085, Hungary.
  • 4. Department of Plant Anatomy, Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/C, Budapest 1117, Hungary.
  • 5. National Biosafety Laboratory, National Public Health Center, Albert Flórián út 2-6, Budapest 1097, Hungary.
  • 6. Femtonics Ltd., Tűzoltó u. 59, Budapest 1094, Hungary.
  • 7. ELKH-ELTE Research Group of Peptide Chemistry, Eötvös Loránd Research Network (ELKH), Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest 1117, Hungary.
PMID: 36857518 DOI: 10.1021/acs.jnatprod.2c00580
Abstract

Diphyllin (1) and justicidin B (2) are arylnaphthalene Lignans with Antiviral and antiproliferative effects. Compound 1 is also known as an effective inhibitor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the in vitro Antiviral and cytotoxic potency of both Lignans in SARS-CoV-2 -infected cells and various Cancer cell lines, respectively, 1 and 2 were isolated from the underground organs of Linum austriacum and Linum perenne. Two previously undescribed arylnaphthalene Lignans, denominated linadiacin A and B (3 and 4), were also isolated and identified. In acidic media, 3 was converted by a two-step reaction into 2 via the intermediate 4. 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 1 and 2 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.