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http://dx.doi.org/10.3347/kjp.2016.54.4.415

Antiplasmodial and Cytotoxic Activities of Toad Venoms from Southern Amazon, Brazil  

Banfi, Felipe Finger (Universidade Federal de Mato Grosso, Instituto de Ciencias da Saude)
Guedes, Karla de Sena (Universidade Federal de Mato Grosso, Instituto de Ciencias da Saude)
Andrighetti, Carla Regina (Universidade Federal de Mato Grosso, Instituto de Ciencias da Saude)
Aguiar, Ana Carolina (Laboratorio de Quimica Medicinal e Experimental, Universidade de Sao Paulo)
Debiasi, Bryan Wender (Universidade Federal de Mato Grosso, Instituto de Ciencias Naturais, Humanas e Sociais)
Noronha, Janaina da Costa (Universidade Federal de Mato Grosso, Instituto de Ciencias Naturais, Humanas e Sociais)
Rodrigues, Domingos de Jesus (Universidade Federal de Mato Grosso, Instituto de Ciencias Naturais, Humanas e Sociais)
Vieira, Gerardo Magela Junior (Universidade Federal do Piaui, Departamento de Quimica)
Sanchez, Bruno Antonio Marinho (Universidade Federal de Mato Grosso, Instituto de Ciencias da Saude)
Publication Information
Parasites, Hosts and Diseases / v.54, no.4, 2016 , pp. 415-421 More about this Journal
Abstract
The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsa-stained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine-resistant Plasmodium falciparum strain, demonstrating lower $IC_{50}$ values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds.
Keywords
Plasmodium falciparum; antiplasmodial effect; toad venom; bufadienolide; malaria chemotherapy;
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1 Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986; 89: 271-277.   DOI
2 Borenfreunda E, Babicha H, Martin-Alguacila N. Comparisons of two in vitro cytotoxicity assays-the neutral red (NR) and tetrazolium MTT tests. Toxicol in Vitro 1988; 2: 1-6.   DOI
3 do Ceu de Madureira M, Paula-Martins A, Gomes M, Paiva J, Proenca da Cunha A, do Rosario V. Antimalarial activity of medicinal plants used in traditional medicine in S. Tome and Principe islands. J Ethnopharmacol 2002; 81: 23-29.   DOI
4 McKerrow JH. Recognition of the role of natural products as drugs to treat neglected tropical diseases by the 2015 Nobel Prize in physiology or medicine. Nat Prod Rep 2015; 32: 1610-1611.   DOI
5 Tu YY, Liang XT. Studies on the constituents of Artemisia annua. Acta Pharma Sin 1981; 16: 366-369 (in Chinese).
6 Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han KT, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ. N Engl J Med 2014; 371: 786.
7 Ait-Mohamed O, Battisti V, Joliot V, Fritsch L, Pontis J, Medjkane S, Redeuilh C, Lamouri A, Fahy C, Rholam M, Atmani D, Ait-Si-Ali S. Acetonic extract of Buxus sempervirens induces cell cycle arrest, apoptosis and autophagy in breast cancer cells. PLoS One 2011; 6: e24537.   DOI
8 Bezivin C, Tomasi S, Lohezic-Le Devehat F, Boustie J. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine 2003; 10: 499-503.   DOI
9 Pink R, Hudson A, Mouries MA, Bendig M. Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov 2005; 4: 727-740.   DOI
10 Dantas GR. Avaliacao da atividade antimalarica de extratos obtidos de algas marinhas no litoral do Rio Grande do Norte. Dissertacao (Mestrado em Ciencias Biologicas), Universidade Federal do Rio Grande do Norte, Natal, RN. 2012. pp 1-72.
11 Cenzi G. Avaliacao da atividade antimalarica e citotoxica de derivados de sulfonamidas e derivados 1,3,4-oxadiazolicos. Dissertacao (Mestrado em Ciencias da Saude), Universidade Federal de Sao Joao Del Rei, Divinopolis, MG. 2013. pp 1-136.
12 Ferreira PMP, Costa-Lotufo LV, Moraes MO, Barros FWA, Martins AMA, Cavalheiro AJ, Bolzani VS, Santos AG, Pessoa C. Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review. Anais Acad Bras Cienc 2011; 83: 1373-1384.   DOI
13 World Health Organization. World Malaria Report: WHO Press; 2014 [cited 2015 March] 2014. Available: http://www.who.int/malaria/publications/world_malaria_report_2014/en/.
14 Fairhurst RM. Understanding artemisinin-resistant malaria: what a difference a year makes. Curr Opin Infect Dis 2015; 28: 417-425.   DOI
15 Rocha AB, Lopes RM, Schwartsmann G. Natural products in anticancer therapy. Curr Opin Pharmacol 2001; 1: 364-369.   DOI
16 Clardy J, Walsh C. Lessons from natural molecules. Nature 2004; 432: 829-837.   DOI
17 Cunha-Filho GA, Resck IS, Cavalcanti BC, Pessoa CO, Moraes MO, Ferreira JR, Rodrigues FA, Dos Santos ML. Cytotoxic profile of natural and some modified bufadienolides from toad Rhinella schneideri parotoid gland secretion. Toxicon 2010; 56: 339-348.   DOI
18 Ferreira PMP, Farias DF, Viana MP, Souza TM, Vasconcelos IM, Soares BM, Pessoa C, Costa-Lotufo LV, Moraes MO, Carvalho AFFU. Study of the antiproliferative potential of seed extracts from Northeastern Brazilian plants. Anais Acad Bras Cienc 2011; 83: 1045-1058.   DOI
19 Vieira Junior GM, Dutra LA, Ferreira PMP, Moraes MO, Costa-Lotufo LV, Pessoa C, Torres RB, Boralle N, Bolzani VS, Cavalheiro AJ. Cytotoxic clerodane diterpenes from Casearia rupestris. J Nat Prod 2011; 74: 776-781.   DOI
20 Militao GCG, Dantas INF, Ferreira PMP, Alves APNN, Chaves DC, Monte FJQ, Pessoa C, Moraes MO, Costa-Lotufo LV. In vitro and in vivo anticancer properties of cucurbitacin isolated from Cayaponia racemosa. Pharm Biol 2012; 50: 1479-1487.   DOI
21 Gao H, Zehl M, Leitner A, Wu X, Zhimin W, Kopp B. Comparison of toad venoms from different Bufo species by HPLC and LCDAD -MS/MS. J Ethnopharmacol 2010; 131: 368-376.   DOI
22 Opie LH, Kowolik H. The discovery of captopril: from large animals to small molecules. Cardiovasc Res 1995; 30: 18-20.   DOI
23 Camargo AC, Ianzer D, Guerreiro JR, Serrano SM. Bradykinin-potentiating peptides: beyond captopril. Toxicon 2012; 59: 516-523.   DOI
24 Harvey AL. Toxins and drug discovery. Toxicon 2014; 92: 193-200.   DOI
25 Pramuk JB. Phylogeny of South American Bufo (Anura: Bufonidae) inferred from combined evidence. Zool J Linn Soc 2006; 146: 407-452.   DOI
26 Frost DR, Grant T, Faivovich J, Bain RH, Haas A, Haddad CFB, de Sa RO, Channing A, Wilkinson M, Donnellan SC, Raxworthy CJ, Campbell JA, Blotto BL, Moler P, Drewes RC, Nussbaum RA, Lynch JD, Green DM, Wheeler WC. The amphibian tree of life. Bull Am Mus Nat Hist 2006; 297: 1-370.   DOI
27 Yang J, Zhang YH, Miao F, Zhou L, Sun W. Two new bufadienolides from the rhizomes of Helleborus thibetanus Franch. Fitoterapia 2010; 81: 636-639.   DOI
28 Ferreira PMP, Lima DJB, Debiasi BW, Soares BM, Machado KC, Noronha JC, Rodrigues DJ, Sinhorin AP, Pessoa C, Junior GMV. Antiproliferative activity of Rhinella marina and Rhaebo guttatus venom extracts from Southern Amazon. Toxicon 2013; 72: 43-51.   DOI
29 Puschett JB, Agunanne E, Uddin MN. Emerging role of the bufadienolides in cardiovascular and kidney diseases. Am J Kidney Dis 2010; 56: 359-370.   DOI
30 Cui X, Inagaki Y, Xu H, Wang D, Qi F, Kokudo N, Fang D, Tang W. Anti-hepatitis B virus activities of cinobufacini and its active components bufalin and cinobufagin in HepG2.2.15 cells. Biol Pharm Bull 2010; 33: 1728-1732.   DOI
31 Kai S, Lu JH, Hui PP, Zhao H. Pre-clinical evaluation of cinobufotalin as a potential anti-lung cancer agent. Biochem Biophys Res Commun 2014; 452: 768-774.   DOI
32 Wang DL, Qi FH, Tang W, Wang FS. Chemical constituents and bioactivities of the skin of Bufo bufo gargarizans Cantor. Chem Biodivers 2011; 8: 559-567.   DOI
33 Delebinski CI, Georgi S, Kleinsimon S, Twardziok M, Kopp B, Melzig MF, Seifert G. Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro. Cell Prolif 2015; 48: 600-610.   DOI
34 Liu C, Cao W, Chen Y, Qu D, Zhou J. Comparison of toad skins Bufo bufo gargarizans Cantor from different regions for their active constituents content and cytotoxic activity on lung carcinoma cell lines. Pharmacogn Mag 2014; 10: 207-212.
35 Gao H, Popescu R, Kopp B, Wang Z. Bufadienolides and their antitumor activity. Nat Prod Rep 2011; 28: 953-969.   DOI
36 Sciani JM, de-Sa-Junior PL, Ferreira AK, Pereira A, Antoniazzi MM, Jared C, Pimenta DC. Cytotoxic and antiproliferative effects of crude amphibian skin secretions on breast tumor cells. Biomed Prev Nutr 2012; 1: 10-18.
37 Lambros C, Vanderberg J. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 1979; 65: 418-420.   DOI
38 Tempone AG, Pimenta DC, Lebrun I, Sartorelli P, Taniwaki NN, de Andrade HF Jr, Antoniazzi MM, Jared C. Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion. Toxicon 2008; 52: 13-21.   DOI
39 Guantai E, Chibale K. How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?. Malar J 2011; 10 (suppl 1): S2.   DOI
40 Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976; 193: 673-675.   DOI