RESUMO
G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures that have gathered significant interest in medicinal chemistry over the past two decades due to their unique structural features and potential roles in a variety of biological processes and disorders. Traditionally, research efforts have focused on stabilizing G4s, while in recent years, the attention has progressively shifted to G4 destabilization, unveiling new therapeutic perspectives. This review provides an in-depth overview of recent advances in the development of small molecules, starting with the controversial role of TMPyP4. Moreover, we described effective metal complexes in addition to G4-disrupting small molecules as well as good G4 stabilizing ligands that can destabilize G4s in response to external stimuli. Finally, we presented antisense strategies as a promising approach for destabilizing G4s, with a particular focus on 2'-OMe antisense oligonucleotide, peptide nucleic acid, and locked nucleic acid. Overall, this review emphasizes the importance of understanding G4 dynamics as well as ongoing efforts to develop selective G4-unfolding strategies that can modulate their biological function and therapeutic potential.
Assuntos
Quadruplex G , Oligonucleotídeos Antissenso , Humanos , Oligonucleotídeos Antissenso/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , LigantesRESUMO
A esquistossomose mansônica é classificada pelo Ministério da Saúde como uma doença negligenciada, causada pelo trematódeo intravascular Schistosoma mansoni. As precárias condições de higiene estão diretamente relacionadas às áreas endêmicas, bem como à pobreza e ao baixo desenvolvimento econômico. Na atualidade, o praziquantel é o fármaco de escolha utilizado para o tratamento dessa patologia. No entanto, o mesmo é relativamente tóxico devido à sua baixa solubilidade, além de relatos acerca de parasitas resistentes ao tratamento. Nesse contexto, faz-se necessário buscar novas alternativas terapêuticas que possam ser utilizadas no tratamento dessa doença. Esta revisão trata da busca por uma nova quimioterapia e sugere a possibilidade de que formas mais adequadas de vetorização de medicamentos já existentes sejam capazes de associar vantagens terapêuticas ao fármaco de escolha para o tratamento proposto, de forma que a população infectada receba seus benefícios.
Manson´s schistosomiasis is classified by the Ministry of Health as a neglected disease caused by the intravascular trematode Schistosoma mansoni. Endemic areas are directly related to poor hygienic conditions, as well as poverty and a low level of economic development. Currently, praziquantel is the drug of choice used to treat this condition, but it is relatively toxic, due to its low solubility, and there are reports of the parasite developing resistance to the treatment. In this context, there is a need to search for new therapeutic agents that can be used to treat this disease. This review covers the search for a new chemotherapy and suggests the possibility that the best existing drug vectorization systems may be able to combine therapeutic advantages with the drug of choice for the treatment, to the benefit of the infected population.