ynthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidate

Autor(es)

Irabuena, Camila ^{[1, 2]} ; Scarone, Laura ^[1] ; Eduardo de Souza, Guilherme ^[3] ; Campos Aguiar, Anna Caroline ^[3] ; Rossi Mendes, Giovana ^[3] ; Carvalho Guido, Rafael Victorio ^[3] ; Serra, Gloria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Republica, Fac Quim, Dept Quim Organ, Quim Farmaceut, Gen Flores 2124, CC1157, Montevideo - Uruguay

^[2] Univ Republica, Fac Quim, Grad Program Chem, Montevideo - Uruguay

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, Ave Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MEDICINAL CHEMISTRY RESEARCH; v. 31, n. 3, p. 426-435, MAR 2022.
• Citações Web of Science: 0

Resumo

During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of ``old{''} drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogs were prepared using two methodologies and evaluated against P. falciparum 3D7. A bithiazole analog, showed attractive inhibitory activity with an EC50 value of 5.9 mu M, low propensity to show toxic effect against HepG2 cells at 25 mu M, and no cross-resistance with standard antimalarials. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/07287-7 - Descoberta de Derivados de Acridina e de Marinoquinolina como Inibidores de Plasmodium falciparum
• Beneficiário: Guilherme Eduardo de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 20/12904-5 - Descoberta de inibidores de Plasmodium falciparum a partir de plantas do Cerrado como candidatos a compostos líderes para a malária: estudos integrados de cromatografia de ultra eficiência, espectroscopia e ensaios biológicos
• Beneficiário: Rafael Victorio Carvalho Guido
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular