Luiza Tamie Hirata Diethelm (Jundiaí / BR), Amanda Bruno da Silva Bellini Ramos (Alfenas / BR), Bruna Inácio Trajano (Campinas / BR), Rafael Dias do Espírito Santo (Campinas / BR), Professor Fábio Antônio Colombo (Alfenas / BR), Professor Marcos José Marques (Alfenas / BR), Professor Carlos Roque Duarte Correia (Campinas / BR), Professor Juliana Quero Reimão (Jundiaí / BR)
Natural products have yielded a diverse array of bioactive compounds, laying the foundation for clinically utilized derivatives. The exploration of natural products derived from marine bacteria has revealed marinoquinolines (MQs), distinguished by a pyrroloquinoline core, showcasing notable in vitro and in vivo anti-Plasmodium activity. Recognizing the imperative to explore novel therapeutic options for toxoplasmosis chemotherapy, this study investigates the potential of MQ derivatives against T. gondii. The study involves the synthesis and characterization of six MQ derivatives, followed by in vitro evaluations on human cells and T. gondii tachyzoites. MQ-1 emerges as the most promising derivative, exhibiting a half-maximal effective concentration (EC50) of 1.46 µM (± 0.45) and a half-maximal cytotoxic concentration (CC50) of 30.51 µM (± 1.80), resulting in a selectivity index (SI) of 20.85. In vivo studies using murine models of acute and chronic toxoplasmosis demonstrate the effectiveness of MQ-1 in reducing parasite burden without observable toxicity. Additionally, the study compares MQ-1 with the standard drug pyrimethamine, showing comparable efficacy in both acute and chronic scenarios. The findings suggest that MQ-1 holds promise as a novel anti-Toxoplasma agent, with potential applications in the treatment of acute and chronic infections. Further research is warranted to explore the full therapeutic potential of MQs and assess their safety profile for future clinical applications. This study provides valuable insights in the quest for new treatment options for toxoplasmosis.