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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: MEDICINAL CHEMISTRY RESEARCH; v. 31, n. 3, p. 426-435, MAR 2022.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/07287-7 - Discovery of Acridine and Marinoquinoline Derivatives as Plasmodium falciparum Inhibitors
• Grantee: Guilherme Eduardo de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/12904-5 - Discovery of Plasmodium falciparum inhibitors from Cerrado plants as lead compounds candidates for malaria: integrated studies of ultra-efficient chromatography, spectroscopy, and biological assays
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants