Scientific and technological prospection of Pilocarpus microphyllus and the alkaloid epiisopiloturine with emphasis on antileishmanial activity

Authors

DOI:

https://doi.org/10.33448/rsd-v10i7.16984

Keywords:

Neglected tropical diseases; Alkaloid; Jaborandi.

Abstract

Leishmaniasis is a parasitic disease that affects populations around the world, especially those in developing countries. Available therapy has serious adverse effects and reports of resistant strains are recurrent. Thus, mapping information on the antiparasitic activity of plants and secondary metabolites for the treatment of leishmaniasis becomes a relevant process for systematizing the studies and technologies developed with these natural products. Thus, this article aimed to carry out a scientific and technological survey of the species Pilocarpus microphyllus and the alkaloid epiisopiloturine (EPI) in databases of publication of articles and patent deposits. For this, the following keywords were used, with the boolean operator AND, in the searches: “Pilocarpus microphyllus”, “epiisopiloturine”, “epiisopiloturine” and “Leishmania amazonensis”. The results showed that most articles and patents involve the keyword “Leishmania amazonensis” (>95% for articles, >89% for patents) and elucidate the search for new therapeutic agents that can replace or enhance the anti-leishmania effect of drugs already used. Searches for the keyword “Pilocarpus microphyllus” show that publications and patents explore the use of the plant and the alkaloids of this jaborandi in biological applications, with only one patent filing using the plant in the treatment of leishmaniasis. For the epiisopiloturine alkaloid, four articles already prove the antiparasitic potential of EPI, and only one patent evidences the application of the alkaloid with antileishmanial activity. Therefore, it is concluded that the researches developed with P. microphyllus and EPI make the scientific and technological scenario promising for the development of antileishmania studies and technologies.

References

Alves, M. M. M., Cruz, L. P. L., Freitas, R. I. C., Costa, A. M. S., Lima, J. E. O., Reis, R. L. R., Véras, L. M. C. & Carvalho, F. A. A. (2018). Essential Oil of Pilocarpus Microphyllus Stapf. Against Promastigotes Forms of Leishmania infantum. Journal of Soil and Plant Biology, 1, 40-43.

Barbosa, M. L. L., Silva, A. V. L. P. N., Vale, L. C., Pimenta, H. B., Veras, L. M. C., Medeiros, J. V. R. & Cerqueira, G. S. (2019). Episopiloturine protected intestinal mucosa from modifications morphological induced by 5‐fluorouracil in mice: The role of cyclooxygenase‐2. The FASEB Journal, 33 (51), 767.34-7676.34.

Berbert, T. R. N., Mello, T. F. P., Nassif, P. W., Mota, C. A., Silveira, A. V., Duarte, G. C., Demarchi, I. G., Aristides, S. M. A., Lonardoni, M. V. C., Teixeira, J. J. V. & Silveira, T. G. V. (2018). Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review. Dermatology Research and Practice, 2018, 1-21.

Botros, S. S. & Bennett, J. L. (2007). Praziquantel resistance. Expert Opinion on Drug Discovery, 2 (1).

Caffrey, C. R. (2007). Chemotherapy of schistosomiasis: present and future. Current Opinion in Chemical Biology, 11, 433–439.

Callahan, D. & Khan, M. A. (2008). 7. AU2006246923 - SISTEMA E MÉTODO PARA PROMOVER O CRESCIMENTO DO CABELO E MELHORAR A SAÚDE DO CABELO E DO COURO CABELUDO. https://patentscope.wipo.int/search/en/detail.jsf?docId=AU181382096&_cid=P21-KNI7UI-23745-1

Caldeira, C. F., Giannini, T. C., Ramos, S. J., Vasconcelos, S., Mitre, S. K., Pires, J. P. A., Ferreira, G. C., Ohashi, S., Mota, J. A., Castilho, A., Siqueira, J. O. & Furtini Neto, A. E. (2017). Sustainability of Jaborandi in the eastern Brazilian Amazon. Perspectives in Ecology and Conservation, 15, 161–171.

Campelo, Y. D. M., Mafud, A. C., Véras, L. M. C., Guimarães, M. A., Yamaguchi, L. F., Lima, D. F., Arcanjo, D. D. R., Kato, M. J., Mendonça, R. Z., Pinto, P. L. S., Mascarenhas, Y. P., Silva, M. P. N., Moraes, J., Eaton, P. & Leite, J. R. S. A. (2017). Synergistic effects of in vitro combinations of piplartine, epiisopiloturine and praziquantel against Schistosoma mansoni. Biomedicine & Pharmacotherapy, 88, 488–499.

Carvalho, L. R., Brito, T. V., C Júnior, J. S., Dias Júnior, G. J., Magalhãres, D. A., Sousa, S. G., Silva, R. O., Silva, F. R. P., Vasconcelos, D. F. P., Véras, L. M. C., Leite, J. R. S. A., Martins, D. S., Martins, C. S., Oliveira, J. S. & Barbosa, A. L. D. R. (2018). Epiisopiloturine, an imidazole alkaloid, reverses inflammation and lipid peroxidation parameters in the Crohn disease model induced by trinitrobenzenosulfonic acid in Wistar rats. Biomedicine & Pharmacotherapy, 102, 278-285.

Castro, K. N., Lima, D. F., Wolschick, D., Andrade, I. M., Santos, R. C., Santos, F. J., Veras, L. M. & Costa-Júnior, L. M. (2016). In vitro effects of Pilocarpus microphyllus extracts and pilocarpine hydrochloride on Rhipicephalus (Boophilus) microplus. Revista Brasileira de Parasitologia Veterinária, 25 (2), 248-253.

Centers for Disease Control and Prevention – CDC. (2021). Neglected Parasitic Infections in the United States. https://www.cdc.gov/parasites/npi/resources/npi_factsheet_18.pdf

Chami, G. F. & Bundy, D. A. P. (2019). More medicines alone cannot ensure the treatment of neglected tropical diseases. The Lancet Infectious Diseases, 19, e330-e336.

Cortez, L. E. R., Ferreira, I. C. P., Lonardoni, V. C., Ferreira, A. G., Vieira, P. C., Silva, M. F. G. F., Fernandes, J. B. & Cortez, D. A. G. (2011). Alkaloids and triterpene from Almeidea coerulea (Nees and Mart.) a. St.-Hil. and anti-leishmanial activity. Brazilian Archives of Biology and Technology, 54 (1), 61-66.

Dutra, R. P., Bezerra, J. L., Silva, M. C. P., Batista, M. C. A., Patrício, F. J. B., Nascimento, F. R. F., Ribeiro, M. N. S. & Guerra, R. N. M. (2019). Antileishmanial activity and chemical composition from Brazilian geopropolis produced by stingless bee Melipona fasciculata. Revista Brasileira de Farmacognosia, 29 (3), 287-293.

Ferreira, C., Passos, C. L. A., Soares, D. C., Costa, K. P., Rezende, M. J. C., Lobão, A. Q., Pinto, A. C., Hamerski, L. & Saraiva, E. M. (2017). Leishmanicidal activity of the alkaloid-rich fraction from Guatteria latifolia. Experimental Parasitology, 172, 51-60.

Ferreira, I. C. P., Lonardoni, M. V. C., Machado, G. M. C., Leon, L. L., Gobbi Filho, L., Pinto, L. H. B. & Oliveira, A. J. B. (2004). Anti-leishmanial activity of alkaloidal extract from Aspidosperma ramiflorum. Memórias do Instituto Oswaldo Cruz, 99 (3), 325-327.

Fuller, L. C., Asiedu, K. B. & Hay, R. J. (2019). Integration of Management Strategies for Skin-Related Neglected Tropical Diseases. Dermatologic Clinics, 39 (1), 147–152.

Gabriel, R. S., Amaral, A. C. F., Lima, I. C., Cruz, J. D., Garcia, A. R., Souza, H. A. S., Adade, C. M., Vermelho, A. B., Alviano, C. S., Alviano, D. S. & Rodrigues, I. A. (2019). β-Carboline-1-propionic acid alkaloid: antileishmanial and cytotoxic effects. Revista Brasileira de Farmacognosia, 29 (6), 755-762.

Gonçalves, S. V. C. B. & Costa, C. H. N. (2018). Treatment of cutaneous leishmaniasis with thermotherapy in Brazil: an

efficacy and safety study. Anais Brasileiros de Dermatologia, 93 (3), 347-55.

Guimarães, M. A., Oliveira, R. N., Véras, L. M., Lima, D. F., Campelo, Y. D., Campos, S. A., Kuckelhaus, S. A., Pinto, P. L., Eaton, P., Mafud, A. C., Mascarenhas, Y. P., Allegretti, S. M., Moraes, J., Lolić, A., Verbić, T. & Leite, J. R. (2015). Anthelmintic activity in vivo of epiisopiloturine against juvenile and adult worms of Schistosoma mansoni. PLOS Neglected Tropical Diseases, 9 (3), e0003656.

Guimarães, M. A., Oliveira, R. N., Almeida, R. L., Mafud, A. C., Sarkis, A. L. V., Ganassin, R., Silva, M. P., Roquini, D. B., Veras, L. M. C., Sawada, T. C. H., Ropke, C. D., Muehlmann, L. A., Joanitti, G. A., Kuckelhaus, S. A. S., Allegretti, S. M., Mascarenhas, Y. P., Moraes, J. & Leite, J. R. S. A. (2018). Epiisopilosine alkaloid has activity against Schistosoma mansoni in mice without acute toxicity. PLoS One, 13, e0196667.

Gütschow, M., Eynde, J. J. V., Jampilek, J., Kang, C., Mangoni, A. A., Fossa, P., Karaman, R., Trabocchi, A., Scott, P. J. H., Reynisson, J., Rapposelli, S., Galdiero, S., Winum, J-Y., Brullo, C., Prokai-Tatrai, K., Sharma, A. K., Schapira, M., Azuma, Y-T., Cerchia, L., Spetea, M., Torri, G., Collina, S., Geronikaki, A., García-Sosa, A. T., Vasconcelos, M. H., Sousa, M. E., Kosalec, I., Tuccinardi, T., Duarte, I. F., Salvador, J. A. R., Bertinaria, M., Pellecchia, M., Amato, J., Rastelli, G., Gomes, P. A. C., Guedes, R. C., Sabatier, J-M., Estévez-Braun, A., Pagano, B., Mangani, S., Ragno, R., Kokotos, G., Brindisi, M., González, F. V., Borges, F., Miloso, M., Rautio, J. & Muñoz-Torrero, D. (2020). Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–7. Molecules, 25 (13).

Kato, L., Oliveira, C. M. A., Faria, E. O., Ribeiro, L. C., Carvalho, B. G., Silva, C. C., Schuquel, I. T. A., Santin, S. M. O., Nakamura, C. V., Britta, E. A., Miranda, N., Iglesias, A. H. & Delprete, P. G. (2012). Antiprotozoal alkaloids from Psychotria prunifolia (Kunth) Steyerm. Journal of the Brazilian Chemical Society, 23 (2), 355-360.

Khalili, S., Ebrahimzade, E., Mohebali, M., Shayan, P., Mohammadi-Yeganeh, S., Moosazadeh Moghaddam, M., Elikaee, S., Akhoundi, B. & Sharifi-Yazdi, M. K. (2019). Investigation of the antimicrobial activity of a short cationic peptide against promastigote and amastigote forms of Leishmania major (MHRO/IR/75/ER): An in vitro study. Experimental Parasitology, 196, p. 48-54.

Koolen, H. H. F., Pral, E. M. F., Alfieri, S. C., Marinho, J. V. N., Serain, A. F., Hernandez-Tasco, A. J., Andreazza, N. L. & Salvador, M. J. (2017). Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis. Phytochemistry, 134, 106-113.

Leite, J. R. S. A., Miura, L. M. C., Lima, D. F., Carneiro, S. L. P., Carvalho, F. A. A., Moraes, J. & Batista, M. C. Z. (2009a). PROCESSO DE OBTENÇÃO DE EPIISOPILOTURINA E SUA APLICAÇÃO NO COMBATE À INFECÇÕES PARASITÁRIAS. https://busca.inpi.gov.br/pePI/servlet/PatenteServletController?Action=detail&CodPedido=812780&SearchParameter=EPIISOPILOTURINA%20%20%20%20%20%20&Resumo=&Titulo=

Leite, J. R. S. A., Miura, L. M. C. V., Fernandes, D. L., Carneiro, S. M. P., Carvalho, F. A. A., Moraes, J. & Batista, M. C. Z. (2009b). processo de obtenção de epiisopiloturina e sua aplicação no combate à infecções parasitárias. https://lp.espacenet.com/publicationDetails/biblio?II=1&ND=3&adjacent=true&locale=pt_LP&FT=D&date=20110531&CC=BR&NR=PI0904110A2&KC=A2

Lima, D. F., Silva, R. A. O., Marques, L. G. A., Véras, L. M. C., Simões, E. R. B., Leite, J. R. S. A., Santos, M. R. M. C. & Pessoa, C. (2015). Prospecção tecnológica do jaborandi (Pilocarpus Microphyllus): espécie economicamente importante no norte e nordeste do Brasil. Revista GEINTEC-Gestão, Inovação e Tecnologias, 5 (1), 1626-1638.

Lima, D. F., Lima, L. I., Rocha, J. A., Andrade, I. M., Grazina, L. G., Villa, C., Meira, L., Véras, L. M., Azevedo, I. F., Biase, A. G., Costa, J., Oliveira, M. B., Mafra, I. & Leite, J. R. (2017). Seasonal change in main alkaloids of jaborandi (Pilocarpus microphyllus Stapf ex Wardleworth), an economically important species from the Brazilian flora. PLoS One, 12 (2), e0170281.

Lombardino, J. & Lowe, J. The role of the medicinal chemist in drug discovery — then and now. (2004). Nature Reviews Drug Discovery, 3, 853–862.

Lucio, E. M. R. A., Rosalen, P. L., Sharapin, N. & Brito, A. R. M. S. Avaliação toxicológica aguda e screening hipocrático da epiisopilosina, alcalóide secundário de Pilocarpus microphyllus Stapf. Revista Brasileira de Farmacognosia, v. 9, n. 10, 2000.

Macêdo, C. G., Fonseca, M. Y. N., Caldeira, A. D., Castro, S. P., Pacienza-Lima, W., Borsodi, M. P. G., Sartoratto, A., Silva, M. N., Salgado, C. G., Rossi-Bergmann, B. & Castro, K. C. F. (2020). Leishmanicidal activity of Piper marginatum Jacq. from Santarém-PA against Leishmania amazonensis. Experimental Parasitology, 210, 107847.

Machado, P. A., Hilário, F. F., Carvalho, L. O., Silveira, M. L., Alves, R. B., Freitas, R. P. & Coimbra, E. S. (2012). Effect of 3-alkylpyridine marine alkaloid analogues in Leishmania species related to American cutaneous leishmaniasis. Chemical Biology & Drug Design, 80 (5), 745-751.

Machín L., Tamargo, B., Piñón, A., Atíes, R. C., Scull, R., Setzer, W. N. & Monzote, L. (2019). Bixa orellana L. (Bixaceae) and Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) Essential Oils Formulated in Nanocochleates against Leishmania amazonensis. Molecules, 24 (23), 4222.

Mäder, P., Rennar, G. A., Ventura, A. M. P., Grevelding, C. G. & Schlitzer, M. (2018). Chemotherapy for Fighting

Schistosomiasis: Past, Present and Future. ChemMedChem, 13 (22), 2374-2389.

Magalhães, K. N., Guarniz, W. A. S., Sá, K. M., Freire, A. B., Monteiro, M. P., Nojosa, R. T., Bieski, I. G. C., Custódio, J. B., Balogun, S. O. & Bandeira, M. A. M. (2019). Medicinal plants of the Caatinga, northeastern Brazil: Ethnopharmacopeia (1980–1990) of the late professor Francisco José de Abreu Matos. Journal of Ethnopharmacology, 237, 314-353.

Mannan, S. B., Elhadad, H., Loc, T. T. H., Sadik, M., Mohamed, M. Y. F., Nam, N. H., Thuong, N. D., Hoang-Trong, B.-L., Duc, N. T. M., Hoang, A. N., Elhusseiny, K. M., Minh, L. H. N., Quynh, T. T. H., Nghia, T. L. B., Nhu, Y. M., Tieu, T. M., Hirayama, K., Huy, N. T. & Hamano, S. (2021). Prevalence and associated factors of asymptomatic leishmaniasis: a systematic review and meta-analysis. Parasitology International, 81, 102229.

Medina, R. P., Schuquel, I. T. A., Pomini, A. M., Silva, C. C., Oliveira, C. M. A., Kato, L., Nakamura, C. V. & Santin, S. M. O. (2016). Ixorine, a New Cyclopeptide Alkaloid from the Branches of Ixora brevifolia. Journal of the Brazilian Chemical Society, 27 (4), 753-758.

Melo, J.G., Amorim, E. L. C. & Albuquerque, U. P. (2009). Native medicinal plants commercialized in Brazil – priorities for conservation. Environmental Monitoring and Assessment, 156, 567-580.

Mendes, N. P., Vieira, I. G. P., Freitas, J. C. C., Guedes, M. I. F. & Morais, S. M. (2018). desenvolvimento de produtos fitoterápicos adjuvantes no tratamento da leishmaniose visceral canina. https://lp.espacenet.com/publicationDetails/biblio?II=3&ND=3&adjacent=true&locale=pt_LP&FT=D&date=20200107&CC=BR&NR=102018009796A2&KC=A2

Morais, S. M., Cossolosso, D. S., Silva, A. A. S., Moraes Filho, M. O., Teixeira, M. J., Campello, C. C., Bonilla, O. H., Paula Júnior, V. F. & Vila-Nova, N. S. (2019). Essential Oils from Croton Species: Chemical Composition, in vitro and in silico Antileishmanial Evaluation, Antioxidant and Cytotoxicity Activities. Journal of the Brazilian Chemical Society, 30 (11), 2404-2412.

Moreira, G., Lima, C., Andrade, D., Rego, N., Passos, I., Moraes, J., Lima, F. & Rocha, J. (2020). Study of metal complexes of ruthenium against schistosomosis: A scientific and technological prospection. Journal of Global Innovation, 2 (1), 1-11.

Moreira, R. K. V. P. P., Lameira, O. A., Campelo, M. F. & Ramires, A. C. S. (2021). Estudo fenológico do germoplasma de Pilocarpus microphyllus Stapf Ex Wardleworth correlacionado com elementos climáticos. Research, Society and Development, 10 (5), e7710514626.

Nicolau, L. A. D., Carvalho, N. S., Pacífico, D. M., Lucetti, L. T., Aragão, K. S., Véras, L. M. C., Souza, M. H. L. P., Leite, J. R. S. A. & Medeiros, J. V. R. (2017). Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats. Biomedicine & Pharmacotherapy, 87, 188-195.

Nunes, T. A. L., Costa, L. H., Sousa, J. M. S., Souza, V. M. R., Rodrigues, R. R. L., Val, M. C. A., Pereira, A. C. T. C.; Ferreira, G. P., Silva, M. V., Costa, J. M. A. R., Véras, L. M. C., Diniz, R. C. & Rodrigues, K. A. F. (2021). Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation. Chemico-Biological Interactions, 339, 109429.

Parra, L. L. L., Bertonha, A. F., Severo, I. R. M., Aguiar, A. C. C., Souza, G. E., Oliva, G., Guido, R. V. C., Grazzia, N., Costa, T. R., Miguel, D. C., Gadelha, F. R., Ferreira, A. G., Hajdu, E., Romo, D. & Berlinck, R. G. S. (2018). Isolation, Derivative Synthesis, and Structure-Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis. Journal of Natural Products, 81 (1), 188-202.

Pereira, M. D. P., Silva, T., Aguiar, A. C. C., Oliva, G., Guido, R. V. C., Yokoyama-Yasunaka, J. K. U., Uliana, S. R. B. & Lopes, L. M. X. (2017). Chemical Composition, Antiprotozoal and Cytotoxic Activities of Indole Alkaloids and Benzofuran Neolignan of Aristolochia cordigera. Planta Medica, 83 (11), 912-920.

Pereira, R. C., Nonato, C. F. A., Camilo, C. J., Coutinho, H. D. M., Rodrigues, F. F. G., Xiao, J. & Costa, J. G. M. (2018). Development and validation of a rapid RP-HPLC-DAD analysis method for the quantification of pilocarpine in Pilocarpus microphyllus (Rutaceae). Food and Chemical Toxicology, 119, 106–111.

Portes, M. C., Moraes, J., Véras, L. M. C., Leite, J. R., Mafud, A. C., Mascarenhas, Y. P., Luz, A. E. V., Lima, F. C. D. A., Nascimento, R. R., Petrilli, H. M., Pinto, P. L. S., Althoff, G. & Ferreira, A. M. C. (2016). Structural and spectroscopic characterization of epiisopiloturine-metal complexes, and anthelmintic activity vs. S. mansoni. Journal of Coordination Chemistry (Print), 69, 01-21.

Powderly, W. G. (2016). Public Policy and Infectious Disease Prevention and Control. Prevention, Policy, and Public Health. Oxford, UK: Oxford University Press.

Raj, S., Sasidharan, S., Balaji, S. N., Dubey, V. K. & Saudagar, P. (2020). Review on natural products as an alternative to contemporary anti‑leishmanial therapeutics. Journal of Proteins and Proteomics, 11, 135-158.

Reuther, G. R. (1991). 1. US5059531 - PROCESSO PARA A PREPARAÇÃO DE PILOCARPINA A PARTIR DE CULTURAS IN VITRO DE PILOCARPUS. https://patentscope.wipo.int/search/en/detail.jsf?docId=US38014749&_cid=P21-KNI7Q6-22667-1

Rocha, J. A., Andrade, I. M., Véras, L. M., Quelemes, P. V., Lima, D. F., Soares, M. J., Pinto, P. L., Mayo, S. J., Ivanova, G., Rangel, M., Correia, M., Mafud, A. C., Mascarenhas, Y. P., Delerue-Matos, C., Moraes, J., Eaton, P. & Leite, J. R. (2017). Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves. Phytotherapy Research, 31 (4), 624-630.

Rocha, J. A., Rego, N. C. S., Carvalho, B. T. S., Silva, F. I., Sousa, J. A., Ramos, R. M., Passos, I. N. G., Moraes, J., Leite, J. R. S. A. & Lima, F. C. A. (2018). Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. PLOS ONE, 13 (6), e0198476.

Rocha, T. M., Machado, N. J., Sousa, J. A. C., Araujo, E. V. O., Guimaraes, M. A., Lima, D. F., Leite, J. R. S. A. & Leal, L. K. A. M. (2019). Imidazole alkaloids inhibit the pro‐inflammatory mechanisms of human neutrophil and exhibit anti‐inflammatory properties in vivo. Journal of Pharmacy and Pharmacology, 71, 849-859.

Rodrigues, J. A., Araújo, A. R., Pitombeira, N. A., Plácido, A., Almeida, M. P., Veras, L. M. C., Delerue-Matos, C., Lima, F. C. D. A., Batagin Neto, A., Paula, R. C. M., Feitosa, J. P. A., Eaton, P., Leite, J. R. S. A. & Silva, D. A. (2019). Acetylated cashew gum-based nanoparticles for the incorporation of alkaloid epiisopiloturine. International Journal of Biological Macromolecules, 128, 965-972.

Rodrigues, R. R. L., Nunes, T. A. L., Araújo, A. R., Marinho Filho, J. D. B., Silva, M. V., Carvalho, F. A. A., Pessoa, O. D. L., Freitas, H. P. S., Rodrigues, K. A. F. & Araújo, A. J. (2021). Antileishmanial activity of cordiaquinone E towards Leishmania (Leishmania) amazonensis. International Immunopharmacology, 90, 1-9.

Salama, I. C., Arrais-Lima, C. & Arrais-Silva, W. W. (2017). Evaluation of Boldine Activity against Intracellular

Amastigotes of Leishmania amazonensis. The Korean Journal of Parasitology, 55 (3), 337-340.

Santos, A. P. & Moreno, P. R. H. (2004). Pilocarpus spp.: A survey of its chemical constituents and biological activities. Revista Brasileira de Ciências Farmacêuticas, 40 (2).

Silva, F. M. A., Koolen, H. H. F., Lima, J. P. S., Santos, D. M. F., Jardim, I. S., Souza, A. D. L. & Pinheiro, M. L. B. (2012). Leishmanicidal activity of fractions rich in aporphine alkaloids from Amazonian Unonopsis species. Revista Brasileira de Farmacognosia, 22 (6), 1368-1371.

Silva, L. A. L., Moraes, M. H., Scotti, M. T., Scotti, L., Souza R. J., Ouete, J. L. N., Biavatti, M. W., Steindel, M. & Sandjo, L. P. (2019). Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential. Parasitology, 146 (7), 849-856

Sousa, P. S. A., Rodrigues, M. G. & Alvarenga, E. M. (2020). Prospecção Tecnológica, com Ênfase nas Atividades Biológicas Nematicida e Larvicida, do Óleo Essencial do Cravo-da-Índia e do Eugenol. Cadernos de Prospecção, 13 (1), 154-170.

Theophile, J. M. (1994). COMPOSIÇÕES COSMÉTICAS COMPREENDENDO OS EXTRATOS DE PILOCARPUS JABORANDI, ALOE VERA. https://worldwide.espacenet.com/patent/search/family/004058058/publication/WO9616667A1?q=pn%3DWO9616667A1

Vallejo, J. C. A., Garcia, A. S. & Soto, R. G. (2018). 15. MX2017001880 - FORMULAÇÃO NUTRACÊUTICA PARA ADMINISTRAÇÃO ORAL DE PILOCARPUS MICROPHYLLUS, LACTOFERRINA E ÓLEO DE PEIXE EM HUMANOS. https://patentscope.wipo.int/search/en/detail.jsf?docId=MX233150202&_cid=P21-KNI7V7-23870-2

Veras, L. M., Guimaraes, M. A., Campelo, Y. D., Vieira, M. M., Nascimento, C., Lima, D. F., Vasconcelos, L., Nakano, E., Kuckelhaus, S. S., Batista, M. C., Leite, J. R. & Moraes, J. (2012). Activity of epiisopiloturine against Schistosoma mansoni. Current Medicinal Chemistry, 19 (13), 2051-2058.

Véras, L. M. C., Cunha, V. R. R., Lima, F. C. D. A., Guimarães, M. A., Vieira, M. M., Campelo, Y. D. M., Sakai, V. Y., Lima, D. F., Carvalho Júnior, P. S., Ellena, J. A., Silva, P. R. P., Vasconcelos, L. C., Godejohann, M., Petrilli, H. M., Constantino, V. R. L., Mascarenhas, Y. P. &Leite, J. R. S. A. (2013). Industrial Scale Isolation, Structural and Spectroscopic Characterization of Epiisopiloturine from Pilocarpus microphyllus Stapf Leaves: A Promising Alkaloid against Schistosomiasis. PLOS ONE, 8 (6), e66702.

Wink, M. (2015). Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines, 2, 251-286.

World Intellectual Property Organization – WIPO. (2020). IPC Publication. https://www.wipo.int/classifications/ipc/ipcpub/?notion=scheme&version=20200101&symbol=none&menulang=en&lang=en&viewmode=f&fipcpc=no&showdeleted=yes&indexes=no&headings=yes&notes=yes&direction=o2n&initial=A&cwid=none&tree=no&searchmode=smart

World Health Organization – WHO. (2020). Leishmaniasis. https://www.who.int/en/news-room/fact-sheets/detail/leishmaniasis

Published

02/07/2021

How to Cite

SOUSA, P. S. de A.; NOGUEIRA, S. S.; AYALA, K. N. R.; SILVA, P. C.; SANTOS, E. da S.; SÁ, R. E. de .; LIMA NETO, F. E. M. de .; LIMA, J. R. da C. .; RODRIGUES, K. A. da F. .; ROCHA, J. A. .; VÉRAS, L. M. C. . Scientific and technological prospection of Pilocarpus microphyllus and the alkaloid epiisopiloturine with emphasis on antileishmanial activity. Research, Society and Development, [S. l.], v. 10, n. 7, p. e59810716984, 2021. DOI: 10.33448/rsd-v10i7.16984. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/16984. Acesso em: 19 apr. 2024.

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Section

Review Article