Planta Med 2013; 79(15): 1440-1446
DOI: 10.1055/s-0033-1350711
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Phenolic Compounds with In Vitro Activity against Respiratory Syncytial Virus from the Nigerian Lichen Ramalina farinacea

Daowan Lai*
1   Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University, Düsseldorf, Germany
,
Damian C. Odimegwu*
2   Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany
3   Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria
,
Charles Esimone
4   Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria
,
Thomas Grunwald
2   Department of Molecular and Medical Virology, Ruhr-University, Bochum, Germany
,
Peter Proksch
1   Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

received 01 April 2013
revised 17 July 2013

accepted 18 July 2013

Publication Date:
22 August 2013 (online)

Abstract

The extract of the Nigerian lichen Ramalina farinacea showed inhibitory activity against the respiratory syncytial virus in a preliminary assay. A follow-up chemical investigation of this lichen led to the isolation of thirteen phenolic compounds (113), including one new hydroquinone depside, designated 5-hydroxysekikaic acid (1), and one new orsellinic acid derivative, 2,3-dihydroxy-4-methoxy-6-pentylbenzoic acid (8). Their structures were unambiguously determined by analysis of 1D and 2D NMR and mass spectroscopic data, as well as by comparison with literature data. Compound 1 was found to partially convert to a 1,4-benzoquinone derivative (1a) during storage. The antiviral activities of the isolated compounds were evaluated against the respiratory syncytial virus. Among them, sekikaic acid (2) showed potent inhibition towards a recombinant strain rg respiratory syncytial virus (IC50 5.69 µg/mL) and respiratory syncytial virus A2 strain (IC50 7.73 µg/mL). The effect of sekikaic acid on the cell viability of HEp2 and Vero cell lines was investigated, and the time of addition assay revealed that sekikaic acid clearly interferes with viral replication at a viral post-entry step, which is over 1.3-fold more active than the control ribavirin at 4 hours postinfection addition. Furthermore, sekikaic acid did not display virucidal activity at concentrations below the TC50, whereas the parental extract did.

* These authors contributed equally to this work.


Supporting Information

 
  • References

  • 1 Empey KM, Peebles Jr RS, Kolls JK. Pharmacologic advances in the treatment and prevention of respiratory syncytial virus. Clin Infect Dis 2010; 50: 1258-1267
  • 2 Nokes JD, Cane PA. New strategies for control of respiratory syncytial virus infection. Curr Opin Infect Dis 2008; 21: 639-643
  • 3 Douglas JL. In search of a small-molecule inhibitor for respiratory syncytial virus. Expert Rev Anti Infect Ther 2004; 2: 625-639
  • 4 Collins PL, Melero JA. Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res 2011; 162: 80-99
  • 5 Molnar K, Farkas E. Current results on biological activities of lichen secondary metabolites: a review. Z Naturforsch 2010; 65c: 157-173
  • 6 Stocker-Worgotter E. Metabolic diversity of lichen-forming ascomycetous fungi: culturing, polyketide and shikimate metabolite production, and PKS genes. Nat Prod Rep 2008; 25: 188-200
  • 7 Pengsuparp T, Cai L, Constant H, Fong HHS, Lin LZ, Kinghorn AD, Pezzuto JM, Cordell GA, Ingolfsdöttir K, Wagner H, Hughes SH. Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse transcriptase. J Nat Prod 1995; 58: 1024-1031
  • 8 Cohen PA, Hudson JB, Towers GHN. Antiviral activities of anthraquinones, bianthrones and hypericin derivatives from lichens. Experientia 1996; 52: 180-183
  • 9 Neamati N, Hong H, Mazumder A, Wang S, Sunder S, Nicklaus MC, Milne GWA, Proksa B, Pommier Y. Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching. J Med Chem 1997; 40: 942-951
  • 10 Esimone CO, Grunwald T, Wildner O, Nchinda G, Tippler B, Proksch P, Überla K. In vitro pharmacodynamic evaluation of antiviral medicinal plants using a vector-based assay technique. J Appl Microbiol 2005; 99: 1346-1355
  • 11 Esimone CO, Grunwald T, Nworu CS, Kuate S, Proksch P, Ueberla K. Broad spectrum antiviral fractions from the lichen Ramalina farinacea (L.) Ach. Chemotherapy 2009; 55: 119-126
  • 12 Molho L, Bodo B, Molho D. 4′-O-Methylnorsekikaic acid, a new meta-depside isolated from a lichen of the genus Ramalina . Phytochemistry 1979; 18: 2049-2051
  • 13 Bendz G, Santesson J, Wachtmeister CA. Studies on the chemistry of lichens. 20. The chemistry of the Ramalina ceruchis group. Acta Chem Scand 1965; 19: 1185-1187
  • 14 Chicita FC. Stenosporic acid, a new depside in Ramalina stenospora . Phytochemistry 1970; 9: 841-844
  • 15 Chester DO, Elix JA. The identification of four new meta-depsides in the lichen Ramalina asahinae . Aust J Chem 1978; 31: 2745-2749
  • 16 Elix J, Wardlaw J. The synthesis of new meta-depsides from Ramalina lichens. Aust J Chem 1986; 39: 227-231
  • 17 Dias DA, Urban S. Phytochemical investigation of the Australian lichens Ramalina glaucescens and Xanthoria parietina . Nat Prod Commun 2009; 4: 959-964
  • 18 Rangaswami S, Rao VS. Chemical components of Ramalina farinacea . Indian J Pharm 1954; 16: 197
  • 19 Rao PS, Shripathy V. Chemical constituents of Umbilicaria indica Frey and Ramalina farinacea L. Ach. Curr Sci 1976; 45: 517-518
  • 20 Chicita FC. The structure of scrobiculin, a new lichen depside in Lobaria scrobiculata and Lobaria amplissima . Phytochemistry 1967; 6: 719-725
  • 21 Elix J, Norfolk S. Synthesis of meta-divarinol and olivetol depsides. Aust J Chem 1975; 28: 399-411
  • 22 Schleich S, Papaioannou M, Baniahmad A, Matusch R. Activity-guided isolation of an antiandrogenic compound of Pygeum africanum . Planta Med 2006; 72: 547-551
  • 23 Schmeda-Hirschmann G, Tapia A, Lima B, Pertino M, Sortino M, Zacchino S, Arias AR, Feresin GE. A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii . Phytother Res 2008; 22: 349-355
  • 24 Lubbe M, Gütlein JP, Reinke H, Langer P. Regioselective synthesis of polyketide-type phenols by formal [3 + 3]-cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with 3-oxoorthoesters. Synlett 2008; 2008: 2671-2673
  • 25 König GM, Wright AD. 1H and 13C-NMR and biological activity investigations of four lichen-derived compounds. Phytochem Anal 1999; 10: 279-284
  • 26 Kouam SF, Ngadjui BT, Krohn K, Wafo P, Ajaz A, Choudhary MI. Prenylated anthronoid antioxidants from the stem bark of Harungana madagascariensis . Phytochemistry 2005; 66: 1174-1179
  • 27 Asakawa Y, Takikawa K, Tori M. Bibenzyl derivatives from the Australian liverwort Frullania falciloba . Phytochemistry 1987; 26: 1023-1025
  • 28 Esimone C, Eck G, Duong T, Uberla K, Proksch P, Grunwald T. Potential anti-respiratory syncytial virus lead compounds from Aglaia species. Pharmazie 2008; 63: 768-773
  • 29 Bruggisser R, Daeniken KV, Jundt G, Schaffner W, Tullberg-Reinert H. Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay. Planta Med 2002; 68: 445-448
  • 30 Kohlmann R, Schwannecke S, Tippler B, Ternette N, Temchura VV, Tenbusch M, Überla K, Grunwald T. Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol 2009; 83: 12601-12610
  • 31 Hallak LK, Collins PL, Knudson W, Peeples ME. Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection. Virology 2000; 271: 264-275
  • 32 Ternette N, Tippler B, Überla K, Grunwald T. Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine 2007; 25: 7271-7279