First Description of Marinoquinoline Derivatives’ Activity against <i>Toxoplasma gondii</i>
Luiza Tamie Hirata Diethelm,
Amanda Bruno da Silva Bellini Ramos,
Giovanna Braga de Lorena,
Bruna Inácio Trajano,
Rafael Dias do Espírito Santo,
Renata Priscila Barros de Menezes,
Marcus Tullius Scotti,
Fabio Antonio Colombo,
Marcos José Marques,
Carlos Roque Duarte Correia,
Juliana Quero Reimão
Affiliations
Luiza Tamie Hirata Diethelm
Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí, Jundiaí 13202-550, Brazil
Amanda Bruno da Silva Bellini Ramos
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas 37130-001, Brazil
Giovanna Braga de Lorena
Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí, Jundiaí 13202-550, Brazil
Bruna Inácio Trajano
Institute of Chemistry, State University of Campinas, Campinas 13083-970, Brazil
Rafael Dias do Espírito Santo
Institute of Chemistry, State University of Campinas, Campinas 13083-970, Brazil
Renata Priscila Barros de Menezes
Programa de Pós-Graduacão em Produtos Naturais e Sintéticos Bioativos (PgPNSB), Instituto de Pesquisa em Fármacos e Medicamentos (IPeFarM), Universidade Federal da Paraíba, João Pessoa 58051-900, Brazil
Marcus Tullius Scotti
Programa de Pós-Graduacão em Produtos Naturais e Sintéticos Bioativos (PgPNSB), Instituto de Pesquisa em Fármacos e Medicamentos (IPeFarM), Universidade Federal da Paraíba, João Pessoa 58051-900, Brazil
Fabio Antonio Colombo
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas 37130-001, Brazil
Marcos José Marques
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas 37130-001, Brazil
Carlos Roque Duarte Correia
Institute of Chemistry, State University of Campinas, Campinas 13083-970, Brazil
Juliana Quero Reimão
Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí, Jundiaí 13202-550, Brazil
Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC50) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC50) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease.