Design, synthesis and optimization of compounds containing the spirochromane core for the treatment of Chagas disease

• Grant number: 23/10715-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2023
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Luiz Carlos Dias
• Grantee: Luiz Fernando Nascimento de Oliveira
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Chagas disease is a neglected tropical disease (NTD), caused by the protozoan Trypanosoma cruzi, which affects 6 million people worldwide and is endemic in our continent. The majority of affected patients reside in Latin America, leaving a trail of sanitary, social, and economic impact in the region. NTDs are characterized by limited investment in research and development (R&D) by major pharmaceutical industries. The only existing antichagasic drugs, benznidazole and nifurtimox, demonstrate low efficacy during the chronic phase of the disease and present high toxicity, making the current treatment unsatisfactory in terms of safety, efficacy, and accessibility. This makes it urgent to discover and develop innovative and safer drugs.Linked to a broad collaborative consortium with the international non-profit R&D organization DNDi (Drugs for Neglected Diseases initiative), the present project aims to plan, synthesize, and optimize analogs with activity against T. cruzi, using modern techniques of organic synthesis, medicinal chemistry, and multiparametric optimization (parasitological activity and physicochemical properties). Initially, the project will be part of early-stage campaigns (hit assessment and hit-to-lead) based on hits provided by DNDi. The results of this project will contribute to the group's efforts in discovering new candidates for antichagasic drugs and advancing collaborative activities between the group, DNDi, and its network of global partners.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VARELA, MARINA T.; DIAS, GLEISTON G.; DE OLIVEIRA, LUIZ FERNANDO N.; DE OLIVEIRA, RAMON G.; AGUIAR, FRANCIELLE D.; NOGUEIRA, JOAO PEDRO; CRUZ, LUIZA R.; DIAS, LUIZ C.. Spirocyclic compounds as innovative tools in drug discovery for medicinal chemists. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 287, p. 23-pg., 2025-04-05. (22/13110-8, 15/50655-9, 22/10577-2, 23/10723-1, 18/24344-4, 23/10715-9)