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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Trypanosoma cruzi-An Update from 2012 to 2021

Author(s): Henrique Barbosa, Fernanda Thevenard, Juliana Quero Reimão, Andre Gustavo Tempone, Kathia Maria Honorio and Joao Henrique Ghilardi Lago*

Volume 23, Issue 3, 2023

Published on: 09 January, 2023

Page: [159 - 213] Pages: 55

DOI: 10.2174/1568026623666221212111514

Price: $65


Background: Chagas disease (American Trypanosomiasis) is classified by the World Health Organization (WHO) as one of the seventeen neglected tropical diseases (NTD), affecting, mainly, several regions of Latin America.

Introduction: However, immigration has expanded the range of this disease to other continents. Thousands of patients with Chagas disease die annually, yet no new therapeutics for Chagas disease have been approved, with only nifurtimox and benznidazole available. Treatment with these drugs presents several challenges, including protozoan resistance, toxicity, and low efficacy. Natural products, including the secondary metabolites found in plants, offer a myriad of complex structures that can be sourced directly or optimized for drug discovery.

Methods: Therefore, this review aims to assess the literature from the last 10 years (2012-2021) and present the anti-T. cruzi compounds isolated from plants in this period, as well as briefly discuss computational approaches and challenges in natural product drug discovery. Using this approach, more than 350 different metabolites were divided based on their biosynthetic pathway alkaloids, terpenoids, flavonoids, polyketides, and phenylpropanoids which displayed activity against different forms of this parasite epimastigote, trypomastigote and more important, the intracellular form, amastigote.

Conclusion: In this aspect, there are several compounds with high potential which could be considered as a scaffold for the development of new drugs for the treatment of Chagas disease-for this, more advanced studies must be performed including pharmacokinetics (PK) and pharmacodynamics (PD) analysis as well as conduction of in vivo assays, these being important limitations in the discovery of new anti-T. cruzi compounds.

Keywords: Trypanosoma cruzi, Chagas disease, Natural products, Terpenoids, Alkaloids, Phenylpropanoids, Quinones, Polyketides.

Graphical Abstract
World Health Organization. Chagas Disease: Control and Elimination. 2010. Available from:
World Health Organization. Chagas disease., Available from: (Accessed on: Apr 9, 2022).
World Health Organization. Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021–2030; World Health Organization: Geneva, 2020.
Echeverría, L.E.; Marcus, R.; Novick, G.; Sosa-Estani, S.; Ralston, K.; Zaidel, E.J.; Forsyth, C.; Ribeiro, A.L.P.; Mendoza, I.; Falconi, M.L.; Mitelman, J.; Morillo, C.A.; Pereiro, A.C.; Pinazo, M.J.; Salvatella, R.; Martinez, F.; Perel, P.; Liprandi, Á.S.; Piñeiro, D.J.; Molina, G.R. WHF IASC roadmap on chagas disease. Glob. Heart, 2020, 15, 26.
Prevention, C.-C. for D.C. and. CDC-Chagas disease-diagnosis. Available from:
Schaub, G.A. An Update on the Knowledge of Parasite–Vector Interactions of Chagas Disease. Res. Rep. Trop. Med., 2021, 12, 63-76.
[] [PMID: 34093053]
CDC. DPDx-American Trypanosomiasis., Available from:
Ferreira, L.L.G.; Andricopulo, A.D. World Chagas Disease Day and the New Road Map for Neglected Tropical Diseases. Curr. Top. Med. Chem., 2020, 20(17), 1518-1520.
[] [PMID: 32830620]
Alonso-Padilla, J.; Cortés-Serra, N.; Pinazo, M.J.; Bottazzi, M.E.; Abril, M.; Barreira, F.; Sosa-Estani, S.; Hotez, P.J.; Gascón, J. Strategies to enhance access to diagnosis and treatment for Chagas disease patients in Latin America. Expert Rev. Anti Infect. Ther., 2019, 17(3), 145-157.
[] [PMID: 30712412]
Toor, J.; Adams, E.R.; Aliee, M.; Amoah, B.; Anderson, R.M.; Ayabina, D.; Bailey, R.; Basáñez, M.G.; Blok, D.J.; Blumberg, S.; Borlase, A.; Rivera, R.C.; Castaño, M.S.; Chitnis, N.; Coffeng, L.E.; Crump, R.E.; Das, A.; Davis, C.N.; Davis, E.L.; Deiner, M.S.; Diggle, P.J.; Fronterre, C.; Giardina, F.; Giorgi, E.; Graham, M.; Hamley, J.I.D.; Huang, C.I.; Kura, K.; Lietman, T.M.; Lucas, T.C.D.; Malizia, V.; Medley, G.F.; Meeyai, A.; Michael, E.; Porco, T.C.; Prada, J.M.; Rock, K.S.; Le Rutte, E.A.; Smith, M.E.; Spencer, S.E.F.; Stolk, W.A.; Touloupou, P.; Vasconcelos, A.; Vegvari, C.; de Vlas, S.J.; Walker, M.; Hollingsworth, T.D. Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation. Clin. Infect. Dis., 2021, 72(8), 1463-1466.
[] [PMID: 32984870]
García-Huertas, P.; Cardona-Castro, N. Advances in the treatment of Chagas disease: Promising new drugs, plants and targets. Biomed. Pharmacother., 2021, 142, 112020.
[] [PMID: 34392087]
Chen, S.L.; Yu, H.; Luo, H.M.; Wu, Q.; Li, C.F.; Steinmetz, A. Conservation and sustainable use of medicinal plants: problems, progress, and prospects. Chin. Med., 2016, 11(1), 37.
[] [PMID: 27478496]
Valli, M.; Bolzani, V.S. Natural Products: Perspectives and Challenges for use of Brazilian Plant Species in the Bioeconomy. An. Acad. Bras. Cienc., 2019, 91(Suppl. 3), e20190208.
[] [PMID: 31411242]
Thomford, N.; Senthebane, D.; Rowe, A.; Munro, D.; Seele, P.; Maroyi, A.; Dzobo, K. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. Int. J. Mol. Sci., 2018, 19(6), 1578.
[] [PMID: 29799486]
Mendoza, N.; Silva, E.M.E. Introduction to phytochemicals: secondary metabolites from plants with active principles for pharmacological importance.Phytochemicals-Source of Antioxidants and Role in Disease Prevention;; Asao, T.; Asaduzzaman, M., Eds.; InTech, 2018.
Velu, G.; Palanichamy, V.; Rajan, A.P. Phytochemical and Pharmacological Importance of Plant Secondary Metabolites in Modern Medicine.Bioorganic Phase in Natural Food: An Overview;; Roopan, S.M.; Madhumitha, G., Eds.; Springer International Publishing: Cham, 2018, pp. 135-156.
Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216.
[] [PMID: 33510482]
Rishton, G.M. Natural products as a robust source of new drugs and drug leads: past successes and present day issues. Am. J. Cardiol., 2008, 101(10), S43-S49.
[] [PMID: 18474274]
Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod., 2020, 83(3), 770-803.
[] [PMID: 32162523]
Ludwiczuk, A.; Skalicka-Woźniak, K.; Georgiev, M.I. Terpenoids. Pharmacognosy; Elsevier, 2017, pp. 233-266.
Biotechnology of isoprenoids. In: Advances in Biochemical Engineering/Biotechnology; Schrader, J.; Bohlmann, J., Eds.; Springer International Publishing: Cham, 2015; p. 148.
Yang, W.; Chen, X.; Li, Y.; Guo, S.; Wang, Z.; Yu, X. Advances in pharmacological activities of terpenoids. Nat. Product Commun., 2020, 15, 1934578X2090355.
Monzote, L.; García, M.; Pastor, J.; Gil, L.; Scull, R.; Maes, L.; Cos, P.; Gille, L. Essential oil from Chenopodium ambrosioides and main components: Activity against Leishmania, their mitochondria and other microorganisms. Exp. Parasitol., 2014, 136, 20-26.
[] [PMID: 24184772]
Andrade, M.A.; Cardoso, M.G.; Gomes, M.S.; Azeredo, C.M.O.; Batista, L.R.; Soares, M.J.; Rodrigues, L.M.A.; Figueiredo, A.C.S. Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis. Braz. J. Microbiol., 2015, 46(1), 189-194.
[] [PMID: 26221107]
Barros, L.; Duarte, A.; Morais-Braga, M.; Waczuk, E.; Vega, C.; Leite, N.; de Menezes, I.; Coutinho, H.; Rocha, J.; Kamdem, J. Chemical Characterization and Trypanocidal, Leishmanicidal and Cytotoxicity Potential of Lantana camara L. (Verbenaceae) Essential Oil. Molecules, 2016, 21(2), 209.
[] [PMID: 26875978]
da Silva, T.B.; Menezes, L.R.A.; Sampaio, M.F.C.; Meira, C.S.; Guimarães, E.T.; Soares, M.B.P.; do Nascimento Prata, A.P.; de Lima Nogueira, P.C.; Costa, E.V. Chemical composition and anti-Trypanosoma cruzi activity of essential oils obtained from leaves of Xylopia frutescens and X. laevigata (Annonaceae). Nat. Prod. Commun., 2013, 8(3), 1934578X1300800.
[] [PMID: 23678822]
Pereira, P.S.; Maia, A.J.; Duarte, A.E.; Oliveira-Tintino, C.D.M.; Tintino, S.R.; Barros, L.M.; Vega-Gomez, M.C.; Rolón, M.; Coronel, C.; Coutinho, H.D.M.; da Silva, T.G. Cytotoxic and anti-kinetoplastid potential of the essential oil of Alpinia speciosa K. Schum. Food Chem. Toxicol., 2018, 119, 387-391.
[] [PMID: 29355623]
Gutiérrez, Y.; Scull, R.; Villa, A.; Satyal, P.; Cos, P.; Monzote, L.; Setzer, W. Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb. Molecules, 2019, 24(8), 1615.
[] [PMID: 31022871]
Gutiérrez, Y.; Montes, R.; Scull, R.; Sánchez, A.; Cos, P.; Monzote, L.; Setzer, W.N. Chemodiversity Associated with Cytotoxicity and Antimicrobial Activity of Piper aduncum var. ossanum. Chem. Biodivers., 2016, 13(12), 1715-1719.
[] [PMID: 27603914]
Dehsheikh, A.B.; Sourestani, M.M.; Dehsheikh, P.B.; Mottaghipisheh, J.; Vitalini, S.; Iriti, M. Monoterpenes: Essential Oil Components with Valuable Features. Mini Rev. Med. Chem., 2020, 20(11), 958-974.
[] [PMID: 31969098]
Natural Products: Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes; Ramawat, K.G.; Mérillon, J.-M; Heidelberg, S.B., Ed.; Berlin, Heidelberg, 2013.
Teles, A.M.; Silva-Silva, J.V.; Fernandes, J.M.P.; Calabrese, K.S.; Abreu-Silva, A.L.; Marinho, S.C.; Mouchrek, A.N.; Filho, V.E.M.; Almeida-Souza, F. Aniba rosaeodora (Var. amazonica Ducke) Essential Oil: Chemical Composition, Antibacterial, Antioxidant and Antitrypanosomal Activity. Antibiotics (Basel), 2020, 10(1), 24.
[] [PMID: 33396612]
Villamizar, L.H.; Cardoso, M.G.; Andrade, J.; Teixeira, M.L.; Soares, M.J. Linalool, a Piper aduncum essential oil component, has selective activity against Trypanosoma cruzi trypomastigote forms at 4°C. Mem. Inst. Oswaldo Cruz, 2017, 112(2), 131-139.
[] [PMID: 28177047]
Tasdemir, D.; Kaiser, M.; Demirci, B.; Demirci, F.; Baser, K.H.C. Antiprotozoal Activity of Turkish Origanum onites Essential Oil and Its Components. Molecules, 2019, 24(23), 4421.
[] [PMID: 31817023]
Menezes, L.R.A.; Santos, N.N.; Meira, C.S.; dos Santos, J.A.F.; Guimarães, E.T.; Soares, M.B.P.; Nepel, A.; Barison, A.; Costa, E.V. A new source of (R)-limonene and rotundifolone from leaves of lippia pedunculosa (verbenaceae) and their trypanocidal properties. Nat. Prod. Commun., 2014, 9, 1934578X1400900.
Santos, L.S.; Fernandes Alves, C.C.; Borges Estevam, E.B.; Gomes Martins, C.H.; de Souza Silva, T.; Rodrigues Esperandim, V.; Dantas Miranda, M.L. Chemical Composition, in vitro Trypanocidal and Antibacterial Activities of the Essential Oil from the Dried Leaves of Eugenia dysenterica DC from Brazil. J. Essent. Oil-Bear. Plants, 2019, 22(2), 347-355.
Da Silveira e Sá, R.C.; Andrade, L.N.; De Sousa, D.P. Sesquiterpenes from essential oils and anti-inflammatory activity. Natural Product Communications, 2015, 10, 1934578X1501001.
Sülsen, V.; Lizarraga, E.; Elso, O.; Cerny, N.; Sanchez Alberti, A.; Bivona, A.; Malchiodi, E.; Cazorla, S.; Catalán, C. Activity of Estafietin and Analogues on Trypanosoma cruzi and Leishmania braziliensis. Molecules, 2019, 24(7), 1209.
[] [PMID: 30925657]
Milagre, M.M.; Branquinho, R.T.; Gonçalves, M.F.; de Assis, G.M.P.; de Oliveira, M.T.; Reis, L.E.S.; Saúde-Guimarães, D.A.; de Lana, M. Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo. Parasitology, 2020, 147(1), 108-119.
[] [PMID: 31455451]
Lima, T.C.; Souza, R.J.; Moraes, M.H.; Steindel, M.; Biavatti, M.W. A New Furanoheliangolide Sesquiterpene Lactone from Calea pinnatifida (R. Br.) Less. (Asteraceae) and Evaluation of Its Trypanocidal and Leishmanicidal Activities. J. Braz. Chem. Soc., 2016.
De Mieri, M.; Monteleone, G.; Ismajili, I.; Kaiser, M.; Hamburger, M. Antiprotozoal Activity-Based Profiling of a Dichloromethane Extract from Anthemis nobilis Flowers. J. Nat. Prod., 2017, 80(2), 459-470.
[] [PMID: 28116906]
Elso, O.G.; Clavin, M.; Hernandez, N.; Sgarlata, T.; Bach, H.; Catalan, C.A.N.; Aguilera, E.; Alvarez, G.; Sülsen, V.P. Antiprotozoal Compounds from Urolepis hecatantha (Asteraceae). Evid. Based Complement. Alternat. Med., 2021, 2021, 6622894.
[] [PMID: 33628303]
Mokoka, T.; Xolani, P.; Zimmermann, S.; Hata, Y.; Adams, M.; Kaiser, M.; Moodley, N.; Maharaj, V.; Koorbanally, N.; Hamburger, M.; Brun, R.; Fouche, G. Antiprotozoal screening of 60 South African plants, and the identification of the antitrypanosomal germacranolides schkuhrin I and II. Planta Med., 2013, 79(14), 1380-1384.
[] [PMID: 23929246]
Galkina, A.; Krause, N.; Lenz, M.; Daniliuc, C.G.; Kaiser, M.; Schmidt, T.J. Antitrypanosomal Activity of Sesquiterpene Lactones from Helianthus tuberosus L. Including a New Furanoheliangolide with an Unusual Structure. Molecules, 2019, 24(6), 1068.
[] [PMID: 30889936]
Laurella, L.C.; Cerny, N.; Bivona, A.E.; Sánchez Alberti, A.; Giberti, G.; Malchiodi, E.L.; Martino, V.S.; Catalan, C.A.; Alonso, M.R.; Cazorla, S.I.; Sülsen, V.P. Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp. PLoS Negl. Trop. Dis., 2017, 11(9), e0005929.
[] [PMID: 28945741]
Ulloa, J.L.; Spina, R.; Casasco, A.; Petray, P.B.; Martino, V.; Sosa, M.A.; Frank, F.M.; Muschietti, L.V. Germacranolide-type sesquiterpene lactones from Smallanthus sonchifolius with promising activity against Leishmania mexicana and Trypanosoma cruzi. Parasit. Vectors, 2017, 10(1), 567.
[] [PMID: 29132413]
Frank, F.M.; Ulloa, J.; Cazorla, S.I.; Maravilla, G.; Malchiodi, E.L.; Grau, A.; Martino, V.; Catalán, C.; Muschietti, L.V. Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation. Evid. Based Complement. Alternat. Med., 2013, 2013, 1-8.
[] [PMID: 23840260]
Bombaça, A.C.S.; Dossow, D.V.; Barbosa, J.M.C.; Paz, C.; Burgos, V.; Menna-Barreto, R.F.S. Trypanocidal activity of natural sesquiterpenoids involves mitochondrial dysfunction, ROS production and autophagic phenotype in Trypanosoma cruzi. Molecules, 2018, 23(11), 2800.
[] [PMID: 30373326]
Sepúlveda-Robles, O.; Espinoza-Gutiérrez, B.; Gomez-Verjan, J.C.; Guzmán-Gutiérrez, S.L.; De Ita, M.; Silva-Miranda, M.; Espitia-Pinzón, C.I.; Fernández-Ramírez, F.; Herrera-Salazar, A.; Mata-Rocha, M.; Ortega-Hernández, A.; Reyes-Chilpa, R. Trypanocidal and toxicological assessment in vitro and in silico of three sesquiterpene lactones from Asteraceae plant species. Food Chem. Toxicol., 2019, 125, 55-61.
[] [PMID: 30572063]
Elso, O.G.; Bivona, A.E.; Sanchez Alberti, A.; Cerny, N.; Fabian, L.; Morales, C.; Catalán, C.A.N.; Malchiodi, E.L.; Cazorla, S.I.; Sülsen, V.P. Trypanocidal activity of four sesquiterpene lactones isolated from asteraceae species. Molecules, 2020, 25(9), 2014.
[] [PMID: 32344932]
Sosa, A.; Salamanca Capusiri, E.; Amaya, S.; Bardón, A.; Giménez-Turba, A.; Vera, N.; Borkosky, S. Trypanocidal activity of south american Vernonieae (Asteraceae) extracts and its sesquiterpene lactones. Nat. Prod. Res., 2021, 35(23), 5224-5228.
[PMID: 32182147]
Cogo, J.; Caleare, A.O.; Ueda-Nakamura, T.; Filho, B.P.D.; Ferreira, I.C.P.; Nakamura, C.V. Trypanocidal activity of guaianolide obtained from Tanacetum parthenium (L.) Schultz-Bip. and its combinational effect with benznidazole. Phytomedicine, 2012, 20(1), 59-66.
[] [PMID: 23069248]
Sülsen, V.P.; Cazorla, S.I.; Frank, F.M.; Laurella, L.C.; Muschietti, L.V.; Catalán, C.A.; Martino, V.S.; Malchiodi, E.L. Natural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatids. PLoS Negl. Trop. Dis., 2013, 7(10), e2494.
[] [PMID: 24130916]
Murakami, C.; Cabral, R.S.; Gomes, K.S.; Costa-Silva, T.A.; Amaral, M.; Romanelli, M.; Tempone, A.G.; Lago, J.H.G. da S. Bolzani, V.; Moreno, P.R.H.; Young, M.C.M. Hedyosulide, a novel trypanosomicidal sesterterpene lactone from Hedyosmum brasiliense Mart. Ex Miq. Phytochem. Lett., 2019, 33, 6-11.
Muñoz, O.M.; Maya, J.D.; Ferreira, J.; Christen, P.; Martin, J.S.; López-Muñoz, R.; Morello, A.; Kemmerling, U. Medicinal plants of Chile: evaluation of their anti-Trypanosoma cruzi activity. Z. Naturforsch. C J. Biosci., 2013, 68(5-6), 198-202.
[] [PMID: 23923616]
de Carvalho, A. da Silva, A.A.; de Sousa, E.A.; Alves Veras, M.D.; Araújo, B.Q.; Thevenard, F.; Lago, J.H.G.; Costa-Silva, T.A.; Tempone, A.G.; Chaves, M.H. In vitro anti-Trypanosoma cruzi evaluation of sesquiterpenes from the branches of Oxandra sessiliflora. Phytochem. Lett., 2020, 37, 59-62.
Londero, V.S.; Costa-Silva, T.A.; Tempone, A.G.; Namiyama, G.M.; Thevenard, F.; Antar, G.M.; Baitello, J.B.; Lago, J.H.G. Anti-Trypanosoma cruzi activity of costic acid isolated from Nectandra barbellata (Lauraceae) is associated with alterations in plasma membrane electric and mitochondrial membrane potentials. Bioorg. Chem., 2020, 95, 103510.
[] [PMID: 31884137]
Morais, T.R.; Costa-Silva, T.A.; Ferreira, D.D.; Novais, B.J.; Torrecilhas, A.C.T.; Tempone, A.G.; Lago, J.H.G. Antitrypanosomal activity and effect in plasma membrane permeability of (−)-bornyl p-coumarate isolated from Piper cernuum (Piperaceae). Bioorg. Chem., 2019, 89, 103001.
[] [PMID: 31129501]
Gonçalves, G.E.G.; Morais, T.R.; Gomes, K.S.; Costa-Silva, T.A.; Tempone, A.G.; Lago, J.H.G.; Caseli, L. Antitrypanosomal activity of epi-polygodial from Drimys brasiliensis and its effects in cellular membrane models at the air-water interface. Bioorg. Chem., 2019, 84, 186-191.
[] [PMID: 30502630]
Albernaz, L.; Deville, A.; Dubost, L.; de Paula, J.; Bodo, B.; Grellier, P.; Espindola, L.; Mambu, L. Spiranthenones A and B, tetraprenylated phloroglucinol derivatives from the leaves of Spiranthera odoratissima. Planta Med., 2012, 78(5), 459-464.
[] [PMID: 22271083]
de Sousa, I.; Sousa Teixeira, M.; Jacometti Cardoso Furtado, N. An overview of biotransformation and toxicity of diterpenes. Molecules, 2018, 23(6), 1387.
[] [PMID: 29890639]
Lozano, E.S.; Spina, R.M.; Tonn, C.E.; Sosa, M.A.; Cifuente, D.A. An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi. Bioorg. Med. Chem. Lett., 2015, 25(23), 5481-5484.
[] [PMID: 26525862]
Bou, D.D.; Tempone, A.G.; Pinto, É.G.; Lago, J.H.G.; Sartorelli, P. Antiparasitic activity and effect of casearins isolated from Casearia sylvestris on Leishmania and Trypanosoma cruzi plasma membrane. Phytomedicine, 2014, 21(5), 676-681.
[] [PMID: 24560122]
Alegre-Gómez, S.; Sainz, P.; Simões, M.F.; Rijo, P.; Moiteiro, C.; González-Coloma, A.; Martínez-Díaz, R.A. Antiparasitic activity of diterpenoids against Trypanosoma cruzi. Planta Med., 2017, 83(3-04), 306-311.
[PMID: 27599261]
Tabefam, M.; Farimani, M.M.; Danton, O.; Ramseyer, J.; Kaiser, M.; Ebrahimi, S.N.; Salehi, P.; Batooli, H.; Potterat, O.; Hamburger, M. Antiprotozoal diterpenes from Perovskia abrotanoides. Planta Med., 2018, 84(12-13), 913-919.
[PMID: 29698984]
Ueno, A.K.; Barcellos, A.F.; Costa-Silva, T.A.; Mesquita, J.T.; Ferreira, D.D.; Tempone, A.G.; Romoff, P.; Antar, G.M.; Lago, J.H.G. Antitrypanosomal activity and evaluation of the mechanism of action of diterpenes from aerial parts of Baccharis retusa (Asteraceae). Fitoterapia, 2018, 125, 55-58.
[] [PMID: 29269235]
Varela, J.; Lavaggi, M.L.; Cabrera, M.; Rodríguez, A.; Miño, P.; Chiriboga, X.; Cerecetto, H.; González, M. Bioactive-guided identification of labdane diterpenoids from aerial parts of Aristeguietia glutinosa as anti-Trypanosoma cruzi agents. Nat. Prod. Commun., 2012, 7, 1934578X1200700.
Mothana, R.; Al-Said, M.; Al-Musayeib, N.; Gamal, A.; Al-Massarani, S.; Al-Rehaily, A.; Abdulkader, M.; Maes, L. In vitro antiprotozoal activity of abietane diterpenoids isolated from Plectranthus barbatus Andr. Int. J. Mol. Sci., 2014, 15(5), 8360-8371.
[] [PMID: 24823881]
Rocha, A.C.F.S.; Morais, G.O.; da Silva, M.M.; Kovatch, P.Y.; Ferreira, D.S.; Esperandim, V.R.; Pagotti, M.C.; Magalhães, L.G.; Heleno, V.C.G. In vitro anti-trypanosomal potential of kaurane and pimarane semi-synthetic derivatives. Nat. Prod. Res., 2022, 36(4), 875-884.
[PMID: 33096959]
Farimani, M.M.; Khodaei, B.; Moradi, H.; Aliabadi, A.; Ebrahimi, S.N.; De Mieri, M.; Kaiser, M.; Hamburger, M. Phytochemical study of Salvia leriifolia roots: rearranged abietane diterpenoids with antiprotozoal activity. J. Nat. Prod., 2018, 81(6), 1384-1390.
[] [PMID: 29896963]
Izumi, E.; Ueda-Nakamura, T.; Veiga, V.F., Jr; Pinto, A.C.; Nakamura, C.V. Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity. J. Med. Chem., 2012, 55(7), 2994-3001.
[] [PMID: 22440015]
Xiao, S.; Tian, Z.; Wang, Y.; Si, L.; Zhang, L.; Zhou, D. Recent progress in the antiviral activity and mechanism study of pentacyclic triterpenoids and their derivatives. Med. Res. Rev., 2018, 38(3), 951-976.
[] [PMID: 29350407]
Furtado, J.C. N.; Pirson, L.; Edelberg, H.; M. Miranda, L.; Loira-Pastoriza, C.; Preat, V.; Larondelle, Y.; André, C. Pentacyclic triterpene bioavailability: an overview of in vitro and in vivo studies. Molecules, 2017, 22, 400.
Ren, Y.; Kinghorn, A.D. Natural product triterpenoids and their semi-synthetic derivatives with potential anticancer activity. Planta Med., 2019, 85(11/12), 802-814.
[] [PMID: 30658371]
Zhou, M.; Zhang, R.H.; Wang, M.; Xu, G.B.; Liao, S.G. Prodrugs of triterpenoids and their derivatives. Eur. J. Med. Chem., 2017, 131, 222-236.
[] [PMID: 28329729]
Morais, T.; da Costa-Silva, T.; Tempone, A.; Borborema, S.; Scotti, M.; de Sousa, R.; Araujo, A.; de Oliveira, A.; de Morais, S.; Sartorelli, P.; Lago, J. Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships. Molecules, 2014, 19(5), 5761-5776.
[] [PMID: 24802987]
de Almeida, B.C.; Araújo, B.Q.; Carvalho, A.A.; Freitas, S.D.L.; Maciel, D.S.A.; Ferreira, A.J.S.; Tempone, A.G.; Martins, L.F.; Alexandre, T.R.; Chaves, M.H.; Lago, J.H.G. Antiprotozoal activity of extracts and isolated triterpenoids of ‘carnauba’ (Copernicia prunifera) wax from Brazil. Pharm. Biol., 2016, 54(12), 3280-3284.
[] [PMID: 27569846]
Tabefam, M.; Moridi Farimani, M.; Danton, O.; Ramseyer, J.; Nejad Ebrahimi, S.; Neuburger, M.; Kaiser, M.; Salehi, P.; Potterat, O.; Hamburger, M. Antiprotozoal isoprenoids from Salvia hydrangea. J. Nat. Prod., 2018, 81(12), 2682-2691.
[] [PMID: 30565934]
Bossolani, G.; Ueda-Nakamura, T.; Silva, S.; Dias Filho, B.; Costa, T.; Quintanilla, R.; Martinez, S.; Veiga-Junior, V.; Pinto, A.; Nakamura, C. Anti-trypanosoma activity and synergistic effects of natural and semi-synthetic triterpenes and predominant cell death through autophagy in amastigote forms. J. Braz. Chem. Soc., 2017, 2017, 103.
Cretton, S.; Bréant, L.; Pourrez, L.; Ambuehl, C.; Perozzo, R.; Marcourt, L.; Kaiser, M.; Cuendet, M.; Christen, P. Chemical constituents from Waltheria indica exert in vitro activity against Trypanosoma brucei and T. cruzi. Fitoterapia, 2015, 105, 55-60.
[] [PMID: 26072041]
Al Musayeib, N.; Mothana, R.; Gamal, A.; Al-Massarani, S.; Maes, L. In vitro antiprotozoal activity of triterpenoid constituents of Kleinia odora growing in Saudi Arabia. Molecules, 2013, 18(8), 9207-9218.
[] [PMID: 23912274]
Bailen, M.; Khamlichi, M.D.; Benharref, A.; Martinez-Diaz, R.A.; Gonzalez-Coloma, A. New bioactive semisynthetic derivatives of 31-norlanostenol and obtusifoliol from Euphorbia officinarum. Nat. Prod. Commun., 2016, 11, 1934578X1601100.
dos Santos, V.; Leite, K.; da Costa Siqueira, M.; Regasini, L.; Martinez, I.; Nogueira, C.; Galuppo, M.; Stolf, B.; Pereira, A.; Cicarelli, R.; Furlan, M.; Graminha, M. Antiprotozoal activity of quinonemethide triterpenes from Maytenus ilicifolia (Celastraceae). Molecules, 2013, 18(1), 1053-1062.
[] [PMID: 23322069]
Kuźma, Ł; Kaiser, M.; Wysokińska, H. The production and antiprotozoal activity of abietane diterpenes in Salvia austriaca hairy roots grown in shake flasks and bioreactor. Prep. Biochem. Biotechnol., 2017, 47(1), 58-66.
[] [PMID: 27070932]
Muganza, D.M.; Fruth, B.; Nzunzu, J.L.; Tuenter, E.; Foubert, K.; Cos, P.; Maes, L.; Kanyanga, R.C.; Exarchou, V.; Apers, S.; Pieters, L. In vitro antiprotozoal activity and cytotoxicity of extracts and isolated constituents from Greenwayodendron suaveolens. J. Ethnopharmacol., 2016, 193, 510-516.
[] [PMID: 27693770]
Meira, C.S.; Guimarães, E.T.; Bastos, T.M.; Moreira, D.R.M.; Tomassini, T.C.B.; Ribeiro, I.M.; Dos Santos, R.R.; Soares, M.B.P. Physalins B and F, seco -steroids isolated from Physalis angulata L., strongly inhibit proliferation, ultrastructure and infectivity of Trypanosoma cruzi. Parasitology, 2013, 140(14), 1811-1821.
[] [PMID: 24001147]
López, D.; Cherigo, L.; Spadafora, C.; Loza-Mejía, M.A.; Martínez-Luis, S. Phytochemical composition, antiparasitic and α–glucosidase inhibition activities from Pelliciera rhizophorae. Chem. Cent. J., 2015, 9(1), 53.
[] [PMID: 26435737]
López-Arencibia, A.; Nicolás-Hernández, D.S.; Bethencourt-Estrella, C.J.; Sifaoui, I.; Reyes-Batlle, M.; Rodríguez-Expósito, R.L.; Rizo-Liendo, A.; Lorenzo-Morales, J.; Bazzocchi, I.L.; Piñero, J.E.; Jiménez, I.A. Withanolides from Withania aristata as antikinetoplastid agents through induction of programmed cell death. Pathogens, 2019, 8(4), 172.
Lemos da Silva, L.A.; Höehr de Moraes, M.; Scotti, M.T.; Scotti, L.; de Jesus Souza, R.; Nantchouang Ouete, J.L.; Biavatti, M.W.; Steindel, M.; Sandjo, L.P. Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential. Parasitology, 2019, 146(7), 849-856.
[] [PMID: 30755289]
Obbo, C.J.D.; Makanga, B.; Mulholland, D.A.; Coombes, P.H.; Brun, R. Antiprotozoal activity of Khaya anthotheca, (Welv.) C.D.C. a plant used by chimpanzees for self-medication. J. Ethnopharmacol., 2013, 147(1), 220-223.
[] [PMID: 23501156]
Dictionary of Alkaloids, 2nd ed; Buckingham, J., Ed.; CRC Press: Boca Raton, FL, 2010.
Debnath, B.; Singh, W.S.; Das, M.; Goswami, S.; Singh, M.K.; Maiti, D.; Manna, K. Role of plant alkaloids on human health: A review of biological activities. Mater. Today Chem., 2018, 9, 56-72.
Lichman, B.R. The scaffold-forming steps of plant alkaloid biosynthesis. Nat. Prod. Rep., 2021, 38(1), 103-129.
[] [PMID: 32745157]
Marella, A.; Tanwar, O.P.; Saha, R.; Ali, M.R.; Srivastava, S.; Akhter, M.; Shaquiquzzaman, M.; Alam, M.M. Quinoline: A versatile heterocyclic. Saudi Pharm. J., 2013, 21(1), 1-12.
[] [PMID: 23960814]
Yun, D.; Yoon, S.Y.; Park, S.J.; Park, Y.J. The anticancer effect of natural plant alkaloid isoquinolines. Int. J. Mol. Sci., 2021, 22(4), 1653.
[] [PMID: 33562110]
Matada, B.S.; Pattanashettar, R.; Yernale, N.G. A comprehensive review on the biological interest of quinoline and its derivatives. Bioorg. Med. Chem., 2021, 32, 115973.
[] [PMID: 33444846]
Shang, X.F.; Morris-Natschke, S.L.; Yang, G.Z.; Liu, Y.Q.; Guo, X.; Xu, X.S.; Goto, M.; Li, J.C.; Zhang, J.Y.; Lee, K.H. Biologically active quinoline and quinazoline alkaloids part II. Med. Res. Rev., 2018, 38(5), 1614-1660.
[] [PMID: 29485730]
Costa, R.S.; Souza Filho, O.P.; Júnior, O.C.S.D.; Silva, J.J.; Hyaric, M.L.; Santos, M.A.V.; Velozo, E.S. In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba. Rev. Bras. Farmacogn., 2018, 28(5), 551-558.
Cretton, S.; Breant, L.; Pourrez, L.; Ambuehl, C.; Marcourt, L.; Ebrahimi, S.N.; Hamburger, M.; Perozzo, R.; Karimou, S.; Kaiser, M.; Cuendet, M.; Christen, P. Antitrypanosomal quinoline alkaloids from the roots of Waltheria indica. J. Nat. Prod., 2014, 77(10), 2304-2311.
[] [PMID: 25314007]
Cretton, S.; Kaiser, M.; Karimou, S.; Ebrahimi, S.N.; Mäser, P.; Cuendet, M.; Christen, P. Pyridine-4(1H)-One alkaloids from Waltheria indica as antitrypanosomatid agents. J. Nat. Prod., 2020, 83(11), 3363-3371.
[] [PMID: 33095014]
Koolen, H.H.F.; Pral, E.M.F.; Alfieri, S.C.; Marinho, J.V.N.; Serain, A.F.; Hernández-Tasco, A.J.; Andreazza, N.L.; Salvador, M.J. Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis. Phytochemistry, 2017, 134, 106-113.
[] [PMID: 27889243]
Tshitenge, D.T.; Bruhn, T.; Feineis, D.; Mudogo, V.; Kaiser, M.; Brun, R.; Bringmann, G. An unusually broad series of seven cyclombandakamines, bridged dimeric naphthylisoquinoline alkaloids from the congolese liana Ancistrocladus ealaensis. Sci. Rep., 2019, 9(1), 9812.
[] [PMID: 31285489]
Bringmann, G.; Seupel, R.; Feineis, D.; Zhang, G.; Xu, M.; Wu, J.; Kaiser, M.; Brun, R.; Seo, E.J.; Efferth, T. Ancistectorine D, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8′- and 7,1′-linked metabolites from the Chinese liana Ancistrocladus tectorius. Fitoterapia, 2016, 115, 1-8.
[] [PMID: 27646602]
Li, J.; Seupel, R.; Feineis, D.; Mudogo, V.; Kaiser, M.; Brun, R.; Brünnert, D.; Chatterjee, M.; Seo, E.J.; Efferth, T.; Bringmann, G. Dioncophyllines C2, D2, and F and related naphthylisoquinoline alkaloids from the congolese liana Ancistrocladus ileboensis with potent activities against Plasmodium falciparum and against multiple myeloma and leukemia cell lines. J. Nat. Prod., 2017, 80(2), 443-458.
[] [PMID: 28121440]
Li, J.; Seupel, R.; Bruhn, T.; Feineis, D.; Kaiser, M.; Brun, R.; Mudogo, V.; Awale, S.; Bringmann, G. Jozilebomines A and B, naphthylisoquinoline dimers from the congolese liana Ancistrocladus ileboensis, with antiausterity activities against the PANC-1 human pancreatic cancer cell line. J. Nat. Prod., 2017, 80(10), 2807-2817.
[] [PMID: 29043798]
González-Coloma, A.; Reina, M.; Sáenz, C.; Lacret, R.; Ruiz-Mesia, L.; Arán, V.J.; Sanz, J.; Martínez-Díaz, R.A. Antileishmanial, antitrypanosomal, and cytotoxic screening of ethnopharmacologically selected Peruvian plants. Parasitol. Res., 2012, 110(4), 1381-1392.
[] [PMID: 21922239]
Barbosa, H.; Costa‐Silva, T.A.; Alves Conserva, G.A.; Araujo, A.J.; Lordello, A.L.L.; Antar, G.M.; Amaral, M.; Soares, M.G.; Tempone, A.G.; Lago, J.H.G. Aporphine alkaloids from Ocotea puberula with anti‐Trypanosoma cruzi potential – activity of dicentrine‐β‐N‐Oxide in the plasma membrane electric potentials. Chem. Biodivers., 2021, 18(4), e2001022.
Barbosa, H.; da Silva, R.L.C.G.; Costa-Silva, T.A.; Tempone, A.G.; Antar, G.M.; Lago, J.H.G.; Caseli, L. Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface. Bioorg. Chem., 2020, 101, 103978.
[] [PMID: 32534347]
Tallini, L.; Andrade, J.; Kaiser, M.; Viladomat, F.; Nair, J.; Zuanazzi, J.; Bastida, J. Alkaloid constituents of the amaryllidaceae plant Amaryllis belladonna L. Molecules, 2017, 22(9), 1437.
[] [PMID: 28858260]
Martinez-Peinado, N.; Cortes-Serra, N.; Torras-Claveria, L.; Pinazo, M.J.; Gascon, J.; Bastida, J.; Alonso-Padilla, J. Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity. Parasit. Vectors, 2020, 13(1), 299.
[] [PMID: 32522289]
Reina, M.; Ruiz-Mesia, L.; Ruiz-Mesia, W.; Sosa-Amay, F.E.; Arevalo-Encinas, L.; González-Coloma, A.; Martínez-Díaz, R. Antiparasitic indole alkaloids from Aspidosperma desmanthum and A. spruceanum from the Peruvian Amazonia. Nat. Prod. Commun., 2014, 9, 1934578X1400900.
Althaus, J.; Kaiser, M.; Brun, R.; Schmidt, T. Antiprotozoal activity of Achillea ptarmica (Asteraceae) and its main alkamide constituents. Molecules, 2014, 19(5), 6428-6438.
[] [PMID: 24853616]
Althaus, J.B.; Malyszek, C.; Kaiser, M.; Brun, R.; Schmidt, T.J. Alkamides from Anacyclus pyrethrum L. and their in vitro antiprotozoal activity. Molecules, 2017, 22(5), 796.
[] [PMID: 28498323]
Veiga-Santos, P.; Desoti, V.C.; Miranda, N.; Ueda-Nakamura, T.; Dias-Filho, B.P.; Silva, S.O.; Cortez, D.A.G.; de Mello, J.C.P.; Nakamura, C.V. The natural compounds piperovatine and piperlonguminine induce autophagic cell death on Trypanosoma cruzi. Acta Trop., 2013, 125(3), 349-356.
[] [PMID: 23228524]
Santos, V.A.F.F.M.; Regasini, L.O.; Nogueira, C.R.; Passerini, G.D.; Martinez, I.; Bolzani, V.S.; Graminha, M.A.S.; Cicarelli, R.M.B.; Furlan, M. Antiprotozoal sesquiterpene pyridine alkaloids from Maytenus ilicifolia. J. Nat. Prod., 2012, 75(5), 991-995.
[] [PMID: 22559947]
Barrosa, K.; Pinto, E.; Tempone, A.; Martins, E.; Lago, J. Alchornedine, a new anti-trypanosomal guanidine alkaloid from Alchornea glandulosa. Planta Med., 2014, 80(15), 1310-1314.
[] [PMID: 25177846]
da Silva, A.; Maciel, D.; Freitas, V.P.; Conserva, G.A.; Alexandre, T.R.; Purisco, S.U.; Tempone, A.G.; Melhem, M.S.; Kato, M.J.; Guimarães, E.F.; Lago, J.H.; Lago, J.H.G. Bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from Piper laevicarpu (Piperaceae). Fitoterapia, 2016, 111, 24-28.
[] [PMID: 27083380]
Cretton, S.; Muñoz, O.; Tapia, J.; Marcourt, L.; Maes, L.; Christen, P. Two new hygroline and tropane alkaloids isolated from Schizanthus hookeri and S. tricolor (Solanaceae). Nat. Prod. Commun., 2017, 12, 1934578X1701200.
García-Huertas, P.; Olmo, F.; Sánchez-Moreno, M.; Dominguez, J.; Chahboun, R.; Triana-Chávez, O. Activity in vitro and in vivo against Trypanosoma cruzi of a furofuran lignan isolated from Piper jericoense. Exp. Parasitol., 2018, 189, 34-42.
[] [PMID: 29656102]
Grecco, S.S.; Costa-Silva, T.A.; Jerz, G.; de Sousa, F.S.; Alves Conserva, G.A.; Mesquita, J.T.; Galuppo, M.K.; Tempone, A.G.; Neves, B.J.; Andrade, C.H.; Cunha, R.L.O.R.; Uemi, M.; Sartorelli, P.; Lago, J.H.G. Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi. Phytomedicine, 2017, 24, 62-67.
[] [PMID: 28160863]
Grecco, S.S.; Costa-Silva, T.A.; Jerz, G.; de Sousa, F.S.; Londero, V.S.; Galuppo, M.K.; Lima, M.L.; Neves, B.J.; Andrade, C.H.; Tempone, A.G.; Lago, J.H.G. Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages. Chem. Biol. Interact., 2017, 277, 55-61.
[] [PMID: 28864277]
Brito, J.R.; da Costa-Silva, T.A.; Tempone, A.G.; Ferreira, E.A.; Lago, J.H.G. Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential. Fitoterapia, 2019, 137, 104251.
[] [PMID: 31271783]
Schmidt, T.J.; Rzeppa, S.; Kaiser, M.; Brun, R. Larrea tridentata—Absolute configuration of its epoxylignans and investigations on its antiprotozoal activity. Phytochem. Lett., 2012, 5(3), 632-638.
Rea, A.; Tempone, A.G.; Pinto, E.G.; Mesquita, J.T.; Rodrigues, E.; Silva, L.G.M.; Sartorelli, P.; Lago, J.H.G. Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial dysfunction. PLoS Negl. Trop. Dis., 2013, 7(12), e2556.
[] [PMID: 24340110]
Rodríguez-Hernández, K.D.; Martínez, I.; Agredano-Moreno, L.T.; Jiménez-García, L.F.; Reyes-Chilpa, R.; Espinoza, B. Coumarins isolated from Calophyllum brasiliense produce ultrastructural alterations and affect in vitro infectivity of Trypanosoma cruzi. Phytomedicine, 2019, 61, 152827.
[] [PMID: 31039535]
Grecco, S. dos S.; Félix, M.J.P.; Lago, J.H.G.; Pinto, É.G.; Tempone, A.G.; Romoff, P.; Ferreira, M.J.P.; Sartorelli, P. Anti-trypanosomal phenolic derivatives from Baccharis uncinella. Natural Product Communications, 2014, 9, 1934578X1400900.
AbouZid, S.F.; Wahba, H.M.; Elshamy, A.; Cos, P.; Maes, L.; Apers, S.; Pieters, L.; Shahat, A.A. Antimicrobial activity of some Clerodendrum species from Egypt. Nat. Prod. Res., 2013, 27(11), 1032-1036.
[] [PMID: 22594542]
Matutino Bastos, T.; Mannochio Russo, H.; Silvio Moretti, N.; Schenkman, S.; Marcourt, L.; Gupta, M.; Wolfender, J.L.; Ferreira Queiroz, E.; Botelho Pereira Soares, M. Chemical constituents of Anacardium occidentale as inhibitors of Trypanosoma cruzi sirtuins. Molecules, 2019, 24(7), 1299.
[] [PMID: 30987092]
Jensen, S.; Omarsdottir, S.; Bwalya, A.G.; Nielsen, M.A.; Tasdemir, D.; Olafsdottir, E.S. Marchantin A, a macrocyclic bisbibenzyl ether, isolated from the liverwort Marchantia polymorpha, inhibits protozoal growth in vitro. Phytomedicine, 2012, 19(13), 1191-1195.
[] [PMID: 22951393]
Santos, R.T.; Hiramoto, L.L.; Lago, J.H.G.; Sartorelli, P.; Tempone, A.G.; Pinto, E.G. Anti-trypanosomal activity of 1,2,3,4,6-penta-O-galloyl-β -D-glucose isolated from Plectranthus barbatus Andrews (Lamiaceae). Quim. Nova, 2012, 35(11), 2229-2332.
Umehara, E.; Costa Silva, T.A.; Mendes, V.M.; Guadagnin, R.C.; Sartorelli, P.; Tempone, A.G.; Lago, J.H.G. Differential lethal action of C17:2 and C17:0 anacardic acid derivatives in Trypanosoma cruzi – A mechanistic study. Bioorg. Chem., 2020, 102, 104068.
[] [PMID: 32653609]
Atay, I.; Kirmizibekmez, H.; Kaiser, M.; Akaydin, G.; Yesilada, E.; Tasdemir, D. Evaluation of in vitro antiprotozoal activity of Ajuga laxmannii and its secondary metabolites. Pharm. Biol., 2016, 54(9), 1808-1814.
[] [PMID: 26734766]
Abreu, L.S.; do Nascimento, Y.M.; do Espirito-Santo, R.F.; Meira, C.S.; Santos, I.P.; Brandão, R.B.; Souto, A.L.; Guedes, M.L.S.; Soares, M.B.P.; Villarreal, C.F.; da Silva, M.S.; Velozo, E.S.; Tavares, J.F. Phenylpropanoids from Croton velutinus with cytotoxic, trypanocidal and anti-inflammatory activities. Fitoterapia, 2020, 145, 104632.
[] [PMID: 32446709]
Lagnika, L.; Weniger, B.; Attioua, B.; Jensen, O.; Anthaume, C.; Sanni, A.; Kaiser, M.; Lobstein, A.; Vonthron-Senecheau, C. Trypanocidal activity of diarylheptanoids from Schrankia leptocarpa DC. S. Afr. J. Bot., 2012, 83, 92-97.
Sandjo, L.P.; de Moraes, M.H.; Kuete, V.; Kamdoum, B.C.; Ngadjui, B.T.; Steindel, M. Individual and combined antiparasitic effect of six plant metabolites against Leishmania amazonensis and Trypanosoma cruzi. Bioorg. Med. Chem. Lett., 2016, 26(7), 1772-1775.
[] [PMID: 26906638]
Morais, T.R.; Romoff, P.; Fávero, O.A.; Reimão, J.Q.; Lourenço, W.C.; Tempone, A.G.; Hristov, A.D.; Di Santi, S.M.; Lago, J.H.G.; Sartorelli, P.; Ferreira, M.J.P. Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae). Parasitol. Res., 2012, 110(1), 95-101.
[] [PMID: 21614544]
Ellendorff, T.; Brun, R.; Kaiser, M.; Sendker, J.; Schmidt, T. PLS-Prediction and confirmation of hydrojuglone glucoside as the antitrypanosomal constituent of Juglans spp. Molecules, 2015, 20(6), 10082-10094.
[] [PMID: 26035104]
Grecco, S.S.; Reimão, J.Q.; Tempone, A.G.; Sartorelli, P.; Cunha, R.L.O.R.; Romoff, P.; Ferreira, M.J.P.; Fávero, O.A.; Lago, J.H.G. In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae). Exp. Parasitol., 2012, 130(2), 141-145.
[] [PMID: 22143090]
da Rocha, C.Q.; Queiroz, E.F.; Meira, C.S.; Moreira, D.R.M.; Soares, M.B.P.; Marcourt, L.; Vilegas, W.; Wolfender, J.L. Dimeric flavonoids from Arrabidaea brachypoda and assessment of their anti-Trypanosoma cruzi activity. J. Nat. Prod., 2014, 77(6), 1345-1350.
[] [PMID: 24871307]
Florencio, M.; Tomás Nery, E.; Rosa, D.; Auxiliadora Nascimento Ribeiro, T.; de Brito Braz Moraes, J.; Araujo Zuma, A.; da Silva Trindade, J.D.; Dutra Barbosa da Rocha, R.F.; Decote-Ricardo, D.; Pinto-da-Silva, L.H.; M Motta, M.C.; de Carvalho, M.G.; Fampa, P. The effect of the biflavonoid 2″3″-dihydroochnaflavone on Trypanosoma cruzi Y strain. Parasitol. Int., 2020, 79, 102180.
[] [PMID: 32860937]
Londero, V.S.; da Costa-Silva, T.A.; Gomes, K.S.; Ferreira, D.D.; Mesquita, J.T.; Tempone, A.G.; Young, M.C.M.; Jerz, G.; Lago, J.H.G. Acetylenic fatty acids from Porcelia macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential. Bioorg. Chem., 2018, 78, 307-311.
[] [PMID: 29625270]
de Á. Santos, L.; Cavalheiro, A.; Tempone, A.; Correa, D.; Alexandre, T.; Quintiliano, N.; Rodrigues-Oliveira, A.; Oliveira-Silva, D.; Martins, R.; Lago, J. Antitrypanosomal acetylene fatty acid derivatives from the seeds of Porcelia macrocarpa (Annonaceae). Molecules, 2015, 20, 8168-8180.
Oliveira, E.A.; Brito, I.A.; Lima, M.L.; Romanelli, M.; Moreira-Filho, J.T.; Neves, B.J.; Andrade, C.H.; Sartorelli, P.; Tempone, A.G.; Costa-Silva, T.A.; Lago, J.H.G. Antitrypanosomal activity of acetogenins isolated from the seeds of Porcelia macrocarpa is associated with alterations in both plasma membrane electric potential and mitochondrial membrane potential. J. Nat. Prod., 2019, 82(5), 1177-1182.
[] [PMID: 31046273]
Conserva, G.A.A.; da Costa-Silva, T.A.; Amaral, M.; Antar, G.M.; Neves, B.J.; Andrade, C.H.; Tempone, A.G.; Lago, J.H.G. Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria. Phytomedicine, 2019, 54, 302-307.
[] [PMID: 30668381]
Al-Massarani, S.; El Gamal, A.; Al-Musayeib, N.; Mothana, R.; Basudan, O.; Al-Rehaily, A.; Farag, M.; Assaf, M.; El Tahir, K.; Maes, L. Phytochemical, antimicrobial and antiprotozoal evaluation of Garcinia mangostana pericarp and α-mangostin, its major xanthone derivative. Molecules, 2013, 18(9), 10599-10608.
[] [PMID: 24002136]
de Oliveira Caleare, A.; Lazarin-Bidóia, D.; Cortez, D.A.G.; Ueda-Nakamura, T.; Dias Filho, B.P.; de Oliveira Silva, S.; Nakamura, C.V. Trypanocidal activity of 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone isolated from Kielmeyera coriacea. Parasitol. Int., 2013, 62(5), 405-411.
[] [PMID: 23680754]
Varela, M.T.; Dias, R.Z.; Martins, L.F.; Ferreira, D.D.; Tempone, A.G.; Ueno, A.K.; Lago, J.H.G.; Fernandes, J.P.S. Gibbilimbol analogues as antiparasitic agents—Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum. Bioorg. Med. Chem. Lett., 2016, 26(4), 1180-1183.
[] [PMID: 26821820]
Acevedo, C.H.; Scotti, L.; Scotti, M.T. In silico studies designed to select sesquiterpene lactones with potential antichagasic activity from an in-house asteraceae database. ChemMedChem, 2018, 13(6), 634-645.
[] [PMID: 29323468]
Gomes, K.S.; da Costa-Silva, T.A.; Oliveira, I.H.; Aguilar, A.M.; Oliveira-Silva, D.; Uemi, M.; Silva, W.A.; Melo, L.R.; Andrade, C.K.Z.; Tempone, A.G.; Baldim, J.L.; Lago, J.H.G. Structure-activity relationship study of antitrypanosomal chalcone derivatives using multivariate analysis. Bioorg. Med. Chem. Lett., 2019, 29(12), 1459-1462.
[] [PMID: 31000155]
Ekins, S.; Lage de Siqueira-Neto, J.; McCall, L.I.; Sarker, M.; Yadav, M.; Ponder, E.L.; Kallel, E.A.; Kellar, D.; Chen, S.; Arkin, M.; Bunin, B.A.; McKerrow, J.H.; Talcott, C. Machine learning models and pathway genome data base for Trypanosoma cruzi drug discovery. PLoS Negl. Trop. Dis., 2015, 9(6), e0003878.
[] [PMID: 26114876]
Scotti, M.; Speck-Planche, A.; Tavares, J.; da Silva, M.D.S.; Cordeiro, M.; Scotti, L. Virtual screening of alkaloids from apocynaceae with potential antitrypanosomal activity. CBIO, 2015, 10, 509-519.
Villalta, F.; Rachakonda, G. Advances in preclinical approaches to Chagas disease drug discovery. Expert Opin. Drug Discov., 2019, 14(11), 1161-1174.
[] [PMID: 31411084]
Kryshchyshyn, A.; Devinyak, O.; Kaminskyy, D.; Grellier, P.; Lesyk, R. Development of predictive QSAR models of 4-thiazolidinones antitrypanosomal activity using modern machine learning algorithms. Mol. Inform., 2018, 37(5), 1700078.
[] [PMID: 29134756]
Luchi, A.M.; Villafañe, R.N.; Gómez Chávez, J.L.; Bogado, M.L.; Angelina, E.L.; Peruchena, N.M. Combining charge density analysis with machine learning tools to investigate the cruzain inhibition mechanism. ACS Omega, 2019, 4(22), 19582-19594.
[] [PMID: 31788588]
de Souza, A.S.; Ferreira, L.L.G.; de Oliveira, A.S.; Andricopulo, A.D. Quantitative structure–activity relationships for structurally diverse chemotypes having anti-Trypanosoma cruzi activity. Int. J. Mol. Sci., 2019, 20(11), 2801.
[] [PMID: 31181717]
Allard, P.M.; Péresse, T.; Bisson, J.; Gindro, K.; Marcourt, L.; Pham, V.C.; Roussi, F.; Litaudon, M.; Wolfender, J.L. integration of molecular networking and in-silico MS/MS fragmentation for natural products dereplication. Anal. Chem., 2016, 88(6), 3317-3323.
[] [PMID: 26882108]
Atanasov, A.G.; Waltenberger, B.; Pferschy-Wenzig, E.M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E.H.; Rollinger, J.M.; Schuster, D.; Breuss, J.M.; Bochkov, V.; Mihovilovic, M.D.; Kopp, B.; Bauer, R.; Dirsch, V.M.; Stuppner, H. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv., 2015, 33(8), 1582-1614.
[] [PMID: 26281720]

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