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

Danilo F. Rodrigues; David A. Maniscalco; Flavia A. J. Silva; Bruna G. Chiari; María V. Castelli; Vera L. B. Isaac; Regina M. B. Cicarelli; Silvia N. López

doi:10.1055/s-0042-112031

Planta Medica, Inhaltsverzeichnis

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

Autor*innen

Danilo F. Rodrigues

¹Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil

²Institute of Chemistry, São Paulo State University, Araraquara, Brazil
David A. Maniscalco

³Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina
Flavia A. J. Silva

¹Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
Bruna G. Chiari

⁴Department of Drugs and Medicaments, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
María V. Castelli

³Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina
Vera L. B. Isaac

⁴Department of Drugs and Medicaments, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil
Regina M. B. Cicarelli

¹Department of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, São Paulo State University, Araraquara, Brazil

²Institute of Chemistry, São Paulo State University, Araraquara, Brazil
Silvia N. López

³Universidad Nacional de Rosario, CONICET, Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina

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

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Referenzen

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
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
3 Pereira PCM, Nazaro EC. Challenges and perspectives of Chagas disease: a review. J Venom Anim Toxins Incl Trop Dis 2013; 19: 34
4 World Health Organization. Technical Report Series 984. Control and surveillance of human African trypanosomiasis. Report of a WHO Expert Committee; 2013
5 World Health Organization. Human African trypanosomiasis. Available at. http://www.who.int/trypanosomiasis_african/en/ Accessed September 28, 2015
6 Brun R, Blum J. Human African trypanosomiasis. Infect Dis Clin North Am 2012; 26: 261-273
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
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
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
10 Agabian N. Trans-splicing of nuclear pre-mRNAs. Cell 1990; 61: 1157-1160
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
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
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
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
15 Ávila HP, Smânia Ede F, Mochache FD, Smânia jr. A. Structure-activity relationship of antibacterial chalcones. Bioorg Med Chem 2008; 16: 9790-9794
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
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
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;
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
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
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
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
23 Burke B, Nair M. Phenylpropene, benzoic acid and flavonoid derivatives from fruits of Jamaican Piper species. Phytochemistry 1986; 25: 1427-1430
24 Ahmed M, Khaleduzzaman M, Rashid M. Chalcone derivatives from Polygonum lapathifolium . Phytochemistry 1981; 20: 2503-2506
25 Ramakrishnan G, Banerji A, Chadha M. Chalcones from Onychium auratum . Phytochemistry 1974; 13: 2317-2318
26 Krishna B, Chaganty R. Cardamonin and alpinetin from seeds of Alpinia speciosa . Phytochemistry 1973; 12: 238
27 Cross GAM, Manning JC. Cultivation of Trypanosoma brucei sspp. in semi defined and defined media. Parasitology 1973; 67: 315-331
28 Wirtz E, Clayton C. Inducible gene expression in trypanosomes mediated by a prokaryotic repressor. Science 1995; 268: 1179-1182
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
30 Trypanosoma cruzi Strain Classification. Available at. http://www.dbbm.fiocruz.br/TcruziDB/strain.html Accessed March 15, 2016
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
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
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
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
35 Wass JA. Origin 7.0. Biotech Software and Internet Report 2002; 3: 130-133
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
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
38 Natarajan AT, Darroudi F. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 1991; 6: 399-403
39 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
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
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
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