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Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2023.tde-29012024-100312
Document
Author
Full name
Anderson Lombardo Noronha
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2023
Supervisor
Committee
Berlinck, Roberto Gomes de Souza (President)
Lago, João Henrique Ghilardi
Nascimento, Isabele Rodrigues
Title in Portuguese
Estudos estruturais e biológicos de alcaloides guanidínicos da esponja Monanchora sp. do litoral do Espírito Santo
Keywords in Portuguese
in vivo
Monanchora
alcaloides guanidinicos
batzelladinas
malária
Abstract in Portuguese
Estudos sobre alcaloides guanidínicos de esponjas marinhas do Brasil ainda são limitados, com a maioria dos compostos isolados já conhecidos. Apenas recentemente foram isolados os primeiros alcaloides guanidínicos inéditos de uma esponja marinha do gênero Monanchora, coletada no litoral do Rio de Janeiro. Estes alcaloides apresentaram potente atividade antiparasitária contra Leishmania infantum e Trypanosoma cruzi. Todavia, a quantidade limitada das substâncias isoladas não permitiu avançar na investigação de atividade antiparasitária in vivo. Em coleta recente realizada no litoral do Espírito Santo, foi possível obter quantidade significativa da esponja Monanchora aff. arbuscula. O presente projeto tem por objetivos avançar no estudo químico e biológico destes alcaloides, tanto no que se refere ao isolamento de alcaloides inéditos quanto no aprofundamento da investigação das atividades biológicas dos alcaloides inéditos e conhecidos in vitro e in vivo. Os alcaloides guanidínicos batzelladina L e batzelladina F apresentaram em estudo anterior, potente atividade in vitro contra a cepa resistente a cloroquina causadora da malária, mostrando ser opções interessantes de estudos in vivo. No presente projeto de mestrado ambos os produtos naturais majoritários da esponja, batzelladina L e F, foram isolados em quantidade suficientes e avaliados in vitro contra a cepa causadora de malária sensível à cloroquina e contra as bactérias multirresistentes a fármacos ESKAPE e apresentaram atividades entre micro e nano molar, a citotoxicidade contra malária também foi avaliada in vitro. Testes in vivo em camundongos infectados foram desenvolvidos com a batzelladina L demonstrando reduzir a parasitemia e prolongar a sobrevivência dos animais frente ao grupo controle.
Title in English
Structural and biological studies of guanidine alkaloids from marine sponge Monanchora sp. from Espírito Santo coast
Keywords in English
in vivo
Monanchora
batzelladine
guanidine alkaloids
malaria
Abstract in English
Studies related to the guanidine alkaloids obtained from marine sponges collected in Brazil are still narrow with the major compounds isolated known. Only recently were isolated new guanidine alkaloids from a marine sponge of genus Monanchora, collected from the Brazilian coast of Rio de Janeiro. Those alkaloids showed potent antiparasitic activity against Leishmania infantum and Trypanosoma cruzi. However, the limited amount of those isolated compounds was insufficient to evaluate their in vivo bioactivity. In a recent collect at Brasilian coast of Espirito Santo, significant amount of the Monanchora aff. arbuscula was obtained. This project has as main objectives to push forward the chemical and biological studies of the guanidine alkaloids, around the isolation of new compounds and to investigate its biological activity, both of the already known alkaloids and eventually of the new ones. The guanidine alkaloids batzelladine L and F had shown in previous studies potent in vitro bioactivity against the chloroquine-resistant malarial pathogen, being an interesting option to be evaluated in vivo. In the present project both majority alkaloids natural products, batzelladine L and F, where isolated from the sponge in sufficient amounts and have their activity in vitro evaluated against the chloroquine-sensitive malarial pathogen and multiresistant bacteria ESKAPE resulting in micro and nano molar activities, the cytotoxicity against malaria where also evaluated in vitro. In vivo experiments on infected mice where developed with batzelladine L, reducing the infection and extending the survival rate of the animals in comparison with the control group.
 
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Publishing Date
2024-01-29
 
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