Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study
Leishmaniasis is recognised as the second largest parasitic disease worldwide and yet a neglected disease. The current pharmacological treatments are associated with significant challenges, including high toxicity, high cost and parasitic resistance. Considering the potential of isopentyl caffeate (...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Current Research in Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590262824000352 |
| _version_ | 1797215889724014592 |
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| author | Wanessa S. Mota Simone S.C. Oliveira Matheus M. Pereira Damião P. Souza Mayara Castro Pollyanna S. Gomes Herbert L.M. Guedes Vinícius F. Souza André L.S. Santos Ricardo L.C. Albuquerque-Junior Juliana C. Cardoso Cristina Blanco-Llamero Sona Jain Eliana B. Souto Patrícia Severino |
| author_facet | Wanessa S. Mota Simone S.C. Oliveira Matheus M. Pereira Damião P. Souza Mayara Castro Pollyanna S. Gomes Herbert L.M. Guedes Vinícius F. Souza André L.S. Santos Ricardo L.C. Albuquerque-Junior Juliana C. Cardoso Cristina Blanco-Llamero Sona Jain Eliana B. Souto Patrícia Severino |
| author_sort | Wanessa S. Mota |
| collection | DOAJ |
| description | Leishmaniasis is recognised as the second largest parasitic disease worldwide and yet a neglected disease. The current pharmacological treatments are associated with significant challenges, including high toxicity, high cost and parasitic resistance. Considering the potential of isopentyl caffeate (ICaf) as an anti-leishmanial agent, the present work evaluated the in vivo toxicity of ICaf and the absorption, distribution, metabolism, and excretion (ADME) properties in silico, aiming at the treatment of Leishmania amazonensis. For the in vivo toxicity testing, Swiss mice (Mus musculus) were treated with a single dose of ICaf. During the 14-day evaluation period, the animals underwent assessments including hippocratic screening, weight measurement, as well as histological and hematological evaluations. Analysis of ADME properties of ICaf was conducted to evaluate its pharmacokinetic characteristics and bioavailability. Characteristics, such as molar refractivity through Lipinski's Rule of Five, were identified. The in silico results showed that ICaf is considered to have good oral bioavailability and has potential to be considered as a new drug. From the in vivo toxicity testing, none of the evaluated parameters revealed toxicity of ICaf to the animals when treated intraperitoneally. The in vivo treatment reduced the lesion and the parasite load at the tested doses, corroborating the assumption that ICaf may be a potential pharmacological alternative against L. amazonensis. |
| first_indexed | 2024-04-24T11:37:15Z |
| format | Article |
| id | doaj.art-60fd8a97f8ed4b53bcdf2cf68dba3645 |
| institution | Directory Open Access Journal |
| issn | 2590-2628 |
| language | English |
| last_indexed | 2024-04-24T11:37:15Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Biotechnology |
| spelling | doaj.art-60fd8a97f8ed4b53bcdf2cf68dba36452024-04-10T04:29:25ZengElsevierCurrent Research in Biotechnology2590-26282024-01-017100209Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo studyWanessa S. Mota0Simone S.C. Oliveira1Matheus M. Pereira2Damião P. Souza3Mayara Castro4Pollyanna S. Gomes5Herbert L.M. Guedes6Vinícius F. Souza7André L.S. Santos8Ricardo L.C. Albuquerque-Junior9Juliana C. Cardoso10Cristina Blanco-Llamero11Sona Jain12Eliana B. Souto13Patrícia Severino14University of Tiradentes (Unit) and Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, BrazilInstitute of Microbiology Paulo de Góes, Department of General Microbiology, Federal University of Rio de Janeiro, (UFRJ), 21941-901 Rio de Janeiro, BrazilUniversity of Coimbra, CERES, Department of Chemical Engineering, Rua Sílvio Lima, Pólo II – Pinhal de Marrocos, 3030-790 Coimbra, PortugalDepartment of Pharmaceutical Sciences, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, BrazilDepartment of Pharmaceutical Sciences, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, BrazilLaboratory of Clinical Immunology, Instituto Oswaldo Cruz - FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, BrazilLaboratory of Clinical Immunology, Instituto Oswaldo Cruz - FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, BrazilLaboratory of Clinical Immunology, Instituto Oswaldo Cruz - FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, BrazilInstitute of Microbiology Paulo de Góes, Department of General Microbiology, Federal University of Rio de Janeiro, (UFRJ), 21941-901 Rio de Janeiro, BrazilPost-Graduating Program in Dentistry, Department of Dentistry, Federal University of Santa Catarina, Florianópolis 88040-370, Brazil; Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis 88040-370, BrazilUniversity of Tiradentes (Unit) and Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, BrazilLaboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria, Ctra Pozuelo-Majadahonda Km 1, 800, 28223, Pozuelo de Alarcón, Madrid, SpainUniversity of Tiradentes (Unit) and Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, BrazilLaboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; Corresponding authors at: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy of University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal. University of Tiradentes (Unit) and Institute of Technology and Research (ITP). Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil.University of Tiradentes (Unit) and Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil; Corresponding authors at: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy of University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal. University of Tiradentes (Unit) and Institute of Technology and Research (ITP). Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil.Leishmaniasis is recognised as the second largest parasitic disease worldwide and yet a neglected disease. The current pharmacological treatments are associated with significant challenges, including high toxicity, high cost and parasitic resistance. Considering the potential of isopentyl caffeate (ICaf) as an anti-leishmanial agent, the present work evaluated the in vivo toxicity of ICaf and the absorption, distribution, metabolism, and excretion (ADME) properties in silico, aiming at the treatment of Leishmania amazonensis. For the in vivo toxicity testing, Swiss mice (Mus musculus) were treated with a single dose of ICaf. During the 14-day evaluation period, the animals underwent assessments including hippocratic screening, weight measurement, as well as histological and hematological evaluations. Analysis of ADME properties of ICaf was conducted to evaluate its pharmacokinetic characteristics and bioavailability. Characteristics, such as molar refractivity through Lipinski's Rule of Five, were identified. The in silico results showed that ICaf is considered to have good oral bioavailability and has potential to be considered as a new drug. From the in vivo toxicity testing, none of the evaluated parameters revealed toxicity of ICaf to the animals when treated intraperitoneally. The in vivo treatment reduced the lesion and the parasite load at the tested doses, corroborating the assumption that ICaf may be a potential pharmacological alternative against L. amazonensis.http://www.sciencedirect.com/science/article/pii/S2590262824000352LeishmaniaIsopentyl caffeateIn silicoPharmacokineticsADMEBioavailability |
| spellingShingle | Wanessa S. Mota Simone S.C. Oliveira Matheus M. Pereira Damião P. Souza Mayara Castro Pollyanna S. Gomes Herbert L.M. Guedes Vinícius F. Souza André L.S. Santos Ricardo L.C. Albuquerque-Junior Juliana C. Cardoso Cristina Blanco-Llamero Sona Jain Eliana B. Souto Patrícia Severino Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study Current Research in Biotechnology Leishmania Isopentyl caffeate In silico Pharmacokinetics ADME Bioavailability |
| title | Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study |
| title_full | Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study |
| title_fullStr | Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study |
| title_full_unstemmed | Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study |
| title_short | Isopentyl caffeate as a promising drug for the treatment of leishmaniasis: An in silico and in vivo study |
| title_sort | isopentyl caffeate as a promising drug for the treatment of leishmaniasis an in silico and in vivo study |
| topic | Leishmania Isopentyl caffeate In silico Pharmacokinetics ADME Bioavailability |
| url | http://www.sciencedirect.com/science/article/pii/S2590262824000352 |
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