Bis-Bibenzyls from the Liverwort Pellia endiviifolia and Their Biological Activity

Based on previous investigations where bis-bibenzyls isolated from liverworts showed various biological activities (cytotoxic, antimicrobial, and antiviral), we investigated their cytotoxic activity in several human cancer cell lines. From the methylene-chloride/methanol extract of the liverwort Pellia endiviifolia, three bis-bibenzyls of the perrottetin type were isolated, namely perrottetin E, 10′-hydroxyperrottetin E, and 10,10′-dihydroxyperrottetin E. The last two were found for the first time in this species. Their structures were resolved using 1D and 2D NMR, as well as by comparison with data in the literature. Cytotoxic activity of the isolated compounds was tested on three human leukemia cell lines, HL-60 (acute promyelocytic leukemia cells), U-937 (acute monocytic leukemia cells), and K-562 (human chronic myelogenous leukemia cells), as well as on human embryonal teratocarcinoma cell line (NT2/D1) and human glioblastoma cell lines A-172 and U-251, and compared to the previously isolated bis-bibenzyls (perrottetins) of similar structure. The isolated compounds exhibited modest activity against leukemia cells and significant activity against NT2/D1 and A-172. Overall, the most active cytotoxic compounds in this investigation were perrottetin E (1), isolated in this work from Pellia endiviifolia, and perrottetin F phenanthrene derivative (7), previously isolated from Lunularia cruciata and added for a comparison of their cytotoxic activity.

[1]  M. Novaković,et al.  Biotransformation of Perrottetin F by Aspergillus niger: New Bioactive Secondary Metabolites , 2021 .

[2]  M. Novaković,et al.  Cytotoxic Activity of Riccardin and Perrottetin Derivatives from the Liverwort Lunularia cruciata. , 2019, Journal of natural products.

[3]  J. Jonczak,et al.  Pellia endiviifolia (Dicks.) Dumort. Liverwort with a Potential for Water Purification , 2018, International Journal of Environmental Research.

[4]  Y. Asakawa,et al.  Chemical Constituents of Bryophytes: Structures and Biological Activity. , 2017, Journal of natural products.

[5]  Y. Asakawa.  The Isolation, Structure Elucidation, and Bio- and Total Synthesis of Bis-bibenzyls, from Liverworts and Their Biological Activity , 2017 .

[6]  Pankaj,et al.  Bryophytes: Hoard of remedies, an ethno-medicinal review , 2016, Journal of traditional and complementary medicine.

[7]  Anuradha Mukherjee,et al.  Therapeutic potential of bryophytes and derived compounds against cancer , 2015 .

[8]  F. Ye,et al.  Identification of U251 glioma stem cells and their heterogeneous stem-like phenotypes , 2013, Oncology letters.

[9]  Y. Asakawa,et al.  Phytochemical and biological studies of bryophytes. , 2013, Phytochemistry.

[10]  Y. Asakawa,et al.  Chemical Constituents of Bryophytes: Bio- and Chemical Diversity, Biological Activity, and Chemosystematics , 2012 .

[11]  H. Lou,et al.  Synthesis of macrocyclic bisbibenzyl derivatives and their anticancer effects as anti-tubulin agents. , 2012, Bioorganic & medicinal chemistry.

[12]  J. Kagan,et al.  Fortschritte der Chemie Organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products , 2012 .

[13]  H. Lou,et al.  Aromatic Compounds from the Liverwort Conocephalum japonicum , 2011, Natural product communications.

[14]  Zu-hua Gao,et al.  Riccardin D, a novel macrocyclic bisbibenzyl, induces apoptosis of human leukemia cells by targeting DNA topoisomerase II , 2012, Investigational New Drugs.

[15]  M. Hennrich,et al.  Syntheses of Macrocyclic Bis(bibenzyl) Compounds Derived from Perrottetin E , 2010 .

[16]  Shang-ming Liu,et al.  Cyclic bisbibenzyls induce growth arrest and apoptosis of human prostate cancer PC3 cells , 2010, Acta Pharmacologica Sinica.

[17]  J. Gu,et al.  Marchantin C: A potential anti-invasion agent in glioma cells , 2010, Cancer biology & therapy.

[18]  Bin Sun,et al.  Synthesis and multidrug resistance reversal activity of dihydroptychantol A and its novel derivatives. , 2009, Bioorganic & medicinal chemistry.

[19]  M. Toyota,et al.  Bryophytes: Bio- and Chemical Diversity, Bioactivity and Chemosystematics , 2009 .

[20]  Xia Li,et al.  Marchantin C, a novel microtubule inhibitor from liverwort with anti-tumor activity both in vivo and in vitro. , 2009, Cancer letters.

[21]  Bin Sun,et al.  Reversal of p-glycoprotein-mediated multidrug resistance by macrocyclic bisbibenzyl derivatives in adriamycin-resistant human myelogenous leukemia (K562/A02) cells. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[22]  Xian-Jun Qu,et al.  Marchantin C, a macrocyclic bisbibenzyl, induces apoptosis of human glioma A172 cells. , 2008, Cancer letters.

[23]  Xian-Jun Qu,et al.  Reversal effect of a macrocyclic bisbibenzyl plagiochin E on multidrug resistance in adriamycin-resistant K562/A02 cells. , 2008, European journal of pharmacology.

[24]  Y. Asakawa.  Biologically active compounds from bryophytes , 2007 .

[25]  H. Lou,et al.  Terpenoids and bisbibenzyls from Chinese liverworts Conocephalum conicum and Dumortiera hirsuta , 2006, Journal of Asian natural products research.

[26]  R. Fleck,et al.  Use of HL-60 Cell Line To Measure Opsonic Capacity of Pneumococcal Antibodies , 2005, Clinical Diagnostic Laboratory Immunology.

[27]  Y. Asakawa.  Recent Advances in Phytochemistry of Bryophytes‐Acetogenins, Terpenoids and Bis(bibenzyl)s from Selected Japanese, Taiwanese, New Zealand, Argentinean and European Liverworts , 2001 .

[28]  Kushal Kumar,et al.  Ethnotherapeutics Of Bryophyte Plagiochasma Appendiculatum Among The Gaddi Tribes Of Kangra Valley, Himachal Pradesh, India , 2000 .

[29]  E. Pandolfi,et al.  Bibenzyl derivatives from Pellia epiphylla , 1997 .

[30]  M. Toyota,et al.  Terpenoids and aromatic compounds from six liverworts , 1996 .

[31]  J. Masters,et al.  Exceptional sensitivity of testicular germ cell tumour cell lines to the new anti-cancer agent, temozolomide. , 1995, British Journal of Cancer.

[32]  Y. Asakawa.  Highlights in phytochemistry of hepaticae-biologically active terpenoids and aromatic compounds , 1994 .

[33]  R. Stephens,et al.  Ohioensins and pallidisetins: novel cytotoxic agents from the moss Polytrichum pallidisetum. , 1994, Journal of natural products.

[34]  Y. Asakawa,et al.  BIS(BIBENZYL) ETHERS FROM PELLIA ENDIVIIFOLIA , 1991 .

[35]  Y. Asakawa.  Chemical Constituents of Hepaticae , 1982 .