PDF herunterladen
Planta Med 2017; 83(03/04): 239-244
DOI: 10.1055/s-0042-112031
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Trypanocidal Activity of Flavokawin B, a Component of Polygonum ferrugineum Wedd

Danilo F. Rodrigues
1   Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
2   Institute of Chemistry, São Paulo State University, Araraquara, Brazil
,
David A. Maniscalco
3   Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina
,
Flavia A. J. Silva
1   Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
,
Bruna G. Chiari
4   Department of Drugs and Medicaments, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
,
María V. Castelli
3   Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina
,
Vera L. B. Isaac
4   Department of Drugs and Medicaments, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
,
Regina M. B. Cicarelli
1   Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
2   Institute of Chemistry, São Paulo State University, Araraquara, Brazil
,
Silvia N. López
3   Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 16. März 2016
revised 26. Juni 2016

accepted 05. Juli 2016

Publikationsdatum:
21. Juli 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

The trypanocidal potential of the natural chalcone flavokawin B, which was isolated from the hexanic extract of Polygonum ferrugineum Wedd., is reported here. Although flavokawin B is widespread, this is the first report about its trypanocidal properties on both Trypanosoma cruzi (IC50 = 9.5 µM, IC50 = 34.7 µM benznidazol, Y strain) epimastigotes and Trypanosoma brucei (IC50 = 4.8 µM, IC50 = 6.4 µM pentamidine, 29–13 strain) procyclic forms, which was also corroborated on T. brucei strain 427 (IC50 = 6.2 µM). In order to learn more about its properties, unspecific cytotoxicity on Hep G2 cells was investigated as well as the trans-splicing inhibitory potential on T. brucei cells. The results shown here point to flavokawin B as a candidate in the search for new agents. It is also cheaper and less toxic than the available drugs to treat trypanosomiasis with a special focus on sleeping sickness disease.

Key words

Trypanosoma cruzi - Trypanosoma brucei - flavokawin B - chalcone - trans-splicing - Polygonum ferrugineum - Polygonaceae
 

  • References

  • 1 Conners EE, Vinetz JM, Weeks JR, Brouwer KC. A global systematic review of Chagas disease prevalence among migrants. Acta Trop 2016; 156: 68-78
    CrossrefPubMedGoogle Scholar
  • 2 Dias JCP, Neto VA, Luna EJA. Mecanismos alternativos de transmissão do Trypanosoma cruzi no Brasil e sugestões para sua prevenção. Rev Soc Bras Med Trop 2011; 44: 375-379
    CrossrefPubMedGoogle Scholar
  • 3 Pereira PCM, Nazaro EC. Challenges and perspectives of Chagas disease: a review. J Venom Anim Toxins Incl Trop Dis 2013; 19: 34
    CrossrefPubMedGoogle Scholar
  • 4 World Health Organization. Technical Report Series 984. Control and surveillance of human African trypanosomiasis. Report of a WHO Expert Committee; 2013
    Google Scholar
  • 5 World Health Organization. Human African trypanosomiasis. Available at. http://www.who.int/trypanosomiasis_african/en/ Accessed September 28, 2015
    PubMedGoogle Scholar
  • 6 Brun R, Blum J. Human African trypanosomiasis. Infect Dis Clin North Am 2012; 26: 261-273
    CrossrefPubMedGoogle Scholar
  • 7 Mair G, Shi H, Li H, Djikeng A, Aviles HO, Bishop JR, Falcone FH, Gavrilescu C, Montgomery JL, Santori MI, Stern LS, Wang Z, Ullu E, Tschudi C. A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA. RNA 2000; 6: 163-169
    CrossrefPubMedGoogle Scholar
  • 8 Ambrósio DL, Lee JH, Panigrahi AK, Nguyen TN, Cicarelli RMB, Günzl A. Spliceosomal proteomics in Trypanosoma brucei reveals new RNA splicing factors. Eukaryot Cell 2009; 8: 990-1000
    CrossrefPubMedGoogle Scholar
  • 9 Denker JA, Zuckerman DM, Maroney PA, Nilsen TW. New components of the spliced leader RNP required for nematode trans-splicing. Nature 2002; 417: 667-670
    CrossrefPubMedGoogle Scholar
  • 10 Agabian N. Trans-splicing of nuclear pre-mRNAs. Cell 1990; 61: 1157-1160
    CrossrefPubMedGoogle Scholar
  • 11 Silva MTA, Ambrósio DL, Trevelin CC, Watanabe TF, Laure HJ, Greene LJ, Rosa JC, Valentini SR, Cicarelli RMB. New insights into trypanosomatid U5 small nuclear ribonucleoproteins. Mem Inst Oswaldo Cruz 2011; 106: 130-138
    PubMedGoogle Scholar
  • 12 López SN, Sierra MG, Gattuso SJ, Furlán RLE, Zacchino SA. An unusual homoisoflavanone and a structurally-related dihydrochalcone from Polygonum ferrugineum (Polygonaceae). Phytochemistry 2006; 67: 2152-2158
    CrossrefPubMedGoogle Scholar
  • 13 López SN, Furlán RLE, Zacchino SA. Detection of antifungal compounds in Polygonum ferrugineum Wedd. extracts by bioassay-guided fractionation. Some evidences of their mode of action. J Ethnopharmacol 2011; 138: 633-636
    CrossrefPubMedGoogle Scholar
  • 14 López SN, Castelli MV, Zacchino SA, Domínguez JN, Lobo G, Charris-Charris J, Cortés JCG, Ribas JC, Devia C, Rodríguez AM, Enriz RD. In vitro antifungal evaluation and structure-activity relationships of a new series of chalcone derivatives and synthetic analogues, with inhibitory properties against polymers of the fungal cell wall. Bioorg Med Chem 2001; 9: 1999-2013
    CrossrefPubMedGoogle Scholar
  • 15 Ávila HP, Smânia Ede F, Mochache FD, Smânia jr. A. Structure-activity relationship of antibacterial chalcones. Bioorg Med Chem 2008; 16: 9790-9794
    CrossrefPubMedGoogle Scholar
  • 16 Sashidhara KV, Avula SR, Mishra V, Palnati GR, Singh LR, Singh N, Chhonker YS, Swamy P, Bhatta RS, Palit G. Identification of quinolinechalcone hybrids as potential antiulcer agents. Eur J Med Chem 2015; 89: 638-653
    CrossrefPubMedGoogle Scholar
  • 17 Sandjo LP, Moraes MH, Kuete V, Kamdoum BC, Ngadjui T, Steindel M. Individual and combined antiparasitic effect of six plant metabolites against Leishmania amazonensis and Trypanosoma cruzi . Bioorg Med Chem Lett 2016; 26: 1772-1775
    CrossrefPubMedGoogle Scholar
  • 18 Venturelli S, Burkard M, Biendl M, Lauer UM, Frank J, Busch C. Prenylated chalcones and flavonoids for the prevention and treatment of cancer. Nutrition 2016; DOI: 10.1016/j.nut.2016.03.020.
    CrossrefPubMedGoogle Scholar
  • 19 Mahapatra DK, Bharti SK, Asati V. Chalcone scaffolds as anti-infective agents: structural and molecular target perspectives. Eur J Med Chem 2015; 101: 496-524
    CrossrefPubMedGoogle Scholar
  • 20 Lunardi F, Guzela M, Rodrigues AT, Corrêa R, Eger-Mangrich E, Steindel M, Grisard EC, Assreuy J, Calixto JB, Santos ARS. Trypanocidal and leishmanicidal properties of substitution-containing chalcones. Antimicrob Agents Chemother 2003; 47: 1449-1451
    CrossrefPubMedGoogle Scholar
  • 21 Troeberg L, Chen X, Flaherty TM, Morty RE, Cheng M, Hua H, Springer C, McKerrow JH, Kenyon GL, Lonsdale-Eccles JD, Coetzer THT, Cohen FE. Chalcone, acyl hydrazide, and related amides kill cultured Trypanosoma brucei brucei . Mol Med 2000; 6: 660-669
    PubMedGoogle Scholar
  • 22 Bray PG, Barrett MP, Ward SA, Koning HP. Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol 2003; 19: 232-239
    CrossrefPubMedGoogle Scholar
  • 23 Burke B, Nair M. Phenylpropene, benzoic acid and flavonoid derivatives from fruits of Jamaican Piper species. Phytochemistry 1986; 25: 1427-1430
    CrossrefPubMedGoogle Scholar
  • 24 Ahmed M, Khaleduzzaman M, Rashid M. Chalcone derivatives from Polygonum lapathifolium . Phytochemistry 1981; 20: 2503-2506
    CrossrefPubMedGoogle Scholar
  • 25 Ramakrishnan G, Banerji A, Chadha M. Chalcones from Onychium auratum . Phytochemistry 1974; 13: 2317-2318
    CrossrefPubMedGoogle Scholar
  • 26 Krishna B, Chaganty R. Cardamonin and alpinetin from seeds of Alpinia speciosa . Phytochemistry 1973; 12: 238
    CrossrefPubMedGoogle Scholar
  • 27 Cross GAM, Manning JC. Cultivation of Trypanosoma brucei sspp. in semi defined and defined media. Parasitology 1973; 67: 315-331
    CrossrefPubMedGoogle Scholar
  • 28 Wirtz E, Clayton C. Inducible gene expression in trypanosomes mediated by a prokaryotic repressor. Science 1995; 268: 1179-1182
    CrossrefPubMedGoogle Scholar
  • 29 Brun R, Schonenberger M. Cultivation and in vitro cloning of procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Acta Trop 1979; 36: 289-292
    PubMedGoogle Scholar
  • 30 Trypanosoma cruzi Strain Classification. Available at. http://www.dbbm.fiocruz.br/TcruziDB/strain.html Accessed March 15, 2016
    PubMedGoogle Scholar
  • 31 Cotinguiba F, Regasini LO, Bolzani VS, Debonsi HM, Passerini GD, Cicarelli RMB, Kato MJ, Furlan M. Piperamides and their derivatives as potential anti-trypanosomal agents. Med Chem Res 2009; 18: 703-711
    CrossrefPubMedGoogle Scholar
  • 32 Castro C, Jimenez M, Gonzalez-de la Parra M. Inhibitory effect of piquerol A on the growth of epimastigotes of Trypanosoma cruzi . Planta Med 1992; 58: 281-282
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 33 Abe F, Nagafugi S, Yamauchi T, Okabe H, Maki J, Higo H, Akahane H, Aguilar A, Jiménez-Estrada M, Reyes-Chilpa R. Trypanocidal constituents in plants 1. Evaluation of some Mexican plants for their trypanocidal activity and active constituents in Guaco, roots of Aristolochia taliscana . Biol Pharm Bull 2002; 25: 1188-1191
    CrossrefPubMedGoogle Scholar
  • 34 Dantas AP, Salomão K, Barbosa HS, Castro SLD. The effect of Bulgarian própolis against Trypanosoma cruzi and during its interaction with host cells. Mem Inst Oswaldo Cruz 2006; 101: 207-211
    CrossrefPubMedGoogle Scholar
  • 35 Wass JA. Origin 7.0. Biotech Software and Internet Report 2002; 3: 130-133
    PubMedGoogle Scholar
  • 36 Muelas-Serrano S, Nogal-Ruiz JJ, Gómez-Barrio A. Setting of a colorimetric method to determine the viability of Trypanosoma cruzi epimastigotes. Parasitol Res 2000; 86: 999-1002
    CrossrefPubMedGoogle Scholar
  • 37 Velásquez AMA, Francisco AI, Kohatsu AA, Silva FA, Rodrigues DF, Teixeira RG, Chiari BG, de Almeida MG, Isaac VL, Vargas MD, Cicarelli RM. Synthesis and tripanocidal activity of ferrocenyl and benzyl diamines against Trypanosoma brucei and Trypanosoma cruzi . Bioorg Med Chem Lett 2014; 24: 1707-1710
    CrossrefPubMedGoogle Scholar
  • 38 Natarajan AT, Darroudi F. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 1991; 6: 399-403
    CrossrefPubMedGoogle Scholar
  • 39 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
    CrossrefPubMedGoogle Scholar
  • 40 Brugginsser R, von Daeniken K, Jundt G, Schaffner W, Tulberg-Reinert H. Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay. Planta Med 2002; 68: 445-448
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 41 Leone E, Morelli E, Di Martino MT, Amodio N, Foresta U, Giullà A, Rossi M, Neri A, Giordano A, Munshi NC, Anderson KC, Tagliaferri P, Tassone P. Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth. Clin Cancer Res 2013; 19: 2096-2106
    CrossrefPubMedGoogle Scholar
  • 42 Michaeli S, Podell D, Agabian N, Ullu E. The 7SL RNA homologue of Trypanosoma brucei is closely related to mammalian 7SL RNA. Mol Biochem Parasitol 1992; 51: 55-64
    CrossrefPubMedGoogle Scholar