Exploração da quimiodiversidade de Urena lobata e Myrsine guianensis através de estratégias analíticas modernas para a descoberta de metabólitos bioativos
Arquivos
Data
2023-12-04
Orientadores
Veiga, Thiago André Moura 
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O relacionamento de diferentes agrupamentos humanos com espécies vegetais tem
origem desde o desenvolvimento das primeiras culturas. Por meio de seus maquinários
enzimáticos, as plantas conseguem biossintetizar uma quantidade inestimável de
substâncias, sendo que a Química de Produtos Naturais acessa tal quimiodiversidade por
meio de ferramentas analíticas. Diante dessas perspectivas, neste trabalho foi realizado o
estudo das espécies Urena lobata e Myrsine guianensis empregando abordagens
integradas, para a busca de metabólitos bioativos em três alvos: leucemia humana,
carcinomas (colorretal e mama) e a busca por ligantes para acetilcolinesterase (AChE). A
partir da análise metabolômica (CLEM)
da fração em diclorometano de U. lobata (ULD)
foi possível anotar 18 metabólitos (u1u18).
Adicionalmente, o desenvolvimento de
métodos de purificação por HPLC permitiu o isolamento e caracterização estrutural de
cinco compostos (u8, u19, u20, u21 e u22). As mesmas estratégias foram conduzidas para
o estudo de M. guianensis, onde a partir do extrato em acetato de etila das folhas (MGA)
da espécie foi possível realizar a anotação 17 compostos (m1m17),
além do isolamento
de cinco substâncias (m1, m2, m3, m5 e m6), sendo que dois destes são inéditos na
literatura: os ácidos myrsinoicos G e H. Na busca por metabólitos citotóxicos, a fração
ULD apresentou EC50 = 36 μg/mL frente a linhagem de leucemia Raji após 24 h de
tratamento. Para as linhagens Kasumi1
e Jurkat, as subfrações
ULD1
a 7, bem como
os extratos de M. guianensis inibiram em até 60 % a proliferação celular após 48 h. Os
compostos u8, u19, u20, u22, m1 e m2 foram testados frente às linhagens Kasumi1,
Jurkart, K562
e KG1, mas não apresentaram efeito citotóxico após 24 h de experimento.
Os compostos u8, u19, u20, u21, u22, m1, m5 e m6 tiveram a sua viabilidade celular
testada frente às linhagens de carcinoma HTT116
e MCF7
por 72 h, onde m6 apresentou
EC50 = 57,87 μM. Como resultado dos ensaios para a identificação de ligantes para AChE
os compostos m1 e m8 foram identificados como ligantes por apresentar razão de
afinidade igual a 4.59 e 81.49, respectivamente.
The historical connection between various human societies and plant species dates back to the early stages of cultural development. Plants, through their enzymatic mechanisms, have the remarkable ability to biosynthesize a vast array of substances, and Natural Products Chemistry leverages this chemical diversity through analytical tools. In this study, Urena lobata and Myrsine guianensis were examined using integrated approaches to identify bioactive metabolites targeting three specific areas: human leukemia, carcinomas (colorectal and breast), and ligands for acetylcholinesterase (AChE). Metabolomic analysis (LCMS) of the dichloromethane fraction of U. lobata (ULD) allowed the annotation of 18 metabolites (u1u18). Furthermore, the development of HPLC purification methods facilitated the isolation and structural characterization of five compounds (u8, u19, u20, u21, and u22). The same strategies were applied to the study of M. guianensis, where the ethyl acetate extract from the leaves (MGA) annotated 17 compounds (m1m17), and five substances (m1, m2, m3, m5, and m6) were isolated, including two novel compounds: myrsinoic acids G and H. In the quest for cytotoxic metabolites, the ULD fraction demonstrated an EC50 of 36 μg/mL against the Raji leukemia cell line after 24 hours of treatment. For the Kasumi1 and Jurkat cell lines, ULD1 to 7 subfractions, along with M. guianensis extracts, inhibited cell proliferation by up to 60% after 48 hours. Compounds u8, u19, u20, u22, m1, and m2 were assessed against Kasumi1, Jurkart, K562, and KG1 cell lines but did not exhibit cytotoxic effects after 24 hours. Compounds u8, u19, u20, u21, u22, m1, m5, and m6 underwent viability testing against HTT116 and MCF7 carcinoma cell lines for 72 hours, where m6 demonstrated an EC50 of 57.87 μM. In the ligand identification assays for AChE, compounds m1 and m8 were recognized as ligands with an affinity ratio of 4.59 and 81.49, respectively.
The historical connection between various human societies and plant species dates back to the early stages of cultural development. Plants, through their enzymatic mechanisms, have the remarkable ability to biosynthesize a vast array of substances, and Natural Products Chemistry leverages this chemical diversity through analytical tools. In this study, Urena lobata and Myrsine guianensis were examined using integrated approaches to identify bioactive metabolites targeting three specific areas: human leukemia, carcinomas (colorectal and breast), and ligands for acetylcholinesterase (AChE). Metabolomic analysis (LCMS) of the dichloromethane fraction of U. lobata (ULD) allowed the annotation of 18 metabolites (u1u18). Furthermore, the development of HPLC purification methods facilitated the isolation and structural characterization of five compounds (u8, u19, u20, u21, and u22). The same strategies were applied to the study of M. guianensis, where the ethyl acetate extract from the leaves (MGA) annotated 17 compounds (m1m17), and five substances (m1, m2, m3, m5, and m6) were isolated, including two novel compounds: myrsinoic acids G and H. In the quest for cytotoxic metabolites, the ULD fraction demonstrated an EC50 of 36 μg/mL against the Raji leukemia cell line after 24 hours of treatment. For the Kasumi1 and Jurkat cell lines, ULD1 to 7 subfractions, along with M. guianensis extracts, inhibited cell proliferation by up to 60% after 48 hours. Compounds u8, u19, u20, u22, m1, and m2 were assessed against Kasumi1, Jurkart, K562, and KG1 cell lines but did not exhibit cytotoxic effects after 24 hours. Compounds u8, u19, u20, u21, u22, m1, m5, and m6 underwent viability testing against HTT116 and MCF7 carcinoma cell lines for 72 hours, where m6 demonstrated an EC50 of 57.87 μM. In the ligand identification assays for AChE, compounds m1 and m8 were recognized as ligands with an affinity ratio of 4.59 and 81.49, respectively.