Potencial biotecnológico da combinação de alcaloides vegetais e de peptídeos antimicrobianos encriptados

• Ano de defesa: 2025
• Autor(a) principal: Cruz, Athamy Sarah de Paula
• Orientador(a): Ramada, Marcelo Henrique Soller
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Católica de Brasília
• Programa de Pós-Graduação: Programa Stricto Sensu em Ciências Genômicas e Biotecnologia
• Departamento: Escola de Saúde e Medicina
• País: Brasil
• Palavras-chave em Português: Alcaloides; Sinergismo; Linhagem celular; Resistência antimicrobiana; Peptídeos antimicrobianos
• Palavras-chave em Inglês: Antimicrobial resistance (AMR); Antimicrobial peptides; Alkaloids; Cell line; Synergy
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS
• Link de acesso: https://bdtd.ucb.br:8443/jspui/handle/tede/3689

Modern medicine faces growing challenges from antimicrobial resistance (AMR), which threatens the effectiveness of established treatments. Overuse of antibiotics has led to the selection of multi-resistant bacteria that are responsible for millions of deaths each year. Faced with this problem, new research has been conducted to find alternatives to conventional antibiotics. Secondary metabolites and peptides are molecules with a wide variety of structures and functions that can not only be antimicrobial but also modulate systemic responses. This study aims to use combinations of plant alkaloids (berberine, sinomenine, tomatidine) and intragenic antimicrobial peptides (Hs02, Gr01) to combat pathogens without conventional antibiotics. The studies evaluated the synergy between these molecules on three axes: antimicrobial activity and hemolytic potential, cell toxicity and healing, and antitumor/antioxidant functions. Results showed synergistic combinations against ATCC strains, reducing effective concentrations up to 128-fold for alkaloids and 4-fold for peptides. In resistant strains, additive effects were observed, with sinomenine standing out, which despite having no previously reported antimicrobial activity, showed additive combinations. Hemolysis and cytotoxicity tests indicated safety for mammalian cells at synergistic concentrations, with cell viability above 70% in human fibroblasts, although they did not show selective toxicity against melanoma. Antioxidant tests showed moderate activity for sinomenine. It is concluded that the proposed combinations offer a promising strategy against resistant infections, with low toxicity and multifunctional activity. However, further studies are needed to explore interaction mechanisms, optimize dosages and evaluate efficacy in in vivo models, with a view to future integrated therapeutic applications.