Studies of structural biology and medicinal chemistry for the discovery and planning of new antimalarial agents

Malaria, caused by protozoan parasites, remains a major global health challenge with high mortality in tropical and subtropical regions. There is an ongoing need for new drugs that are more effective, less toxic, and easier to administer. Among potential targets, Plasmodium falciparum enolase (Pfen) has emerged as a critical biomolecule. It plays an essential role in the parasite’s glycolytic pathway—its primary source of energy—and has also been detected in various subcellular compartments, including the cytosol, nucleus, plasma membrane, vacuole, and cytoskeleton. These diverse localizations suggest that Pfen may perform additional “moonlighting” functions unrelated to glycolysis, increasing its appeal as a molecular target for antimalarial drug development. The project has been structured in two distinct phases. The first phase focuses on basic research, aiming to elucidate the molecular features that govern the structure, function, and recognition mechanisms of Pfen. This foundational knowledge will help assess its suitability and behavior as a drug target. The second phase involves applied research and is intended to leverage the molecular insights gained in the first stage to identify and develop promising chemotherapeutic candidates for malaria. To achieve this, the study incorporates multiple strategies spanning structural biology—such as protein expression, purification, crystallization, and 3D structure elucidation—and medicinal chemistry, including in vitro and in vivo biological screening, molecular modeling, and structure–activity relationship studies. The research will be conducted at the Center for Research and Innovation in Biodiversity and Drugs (CIBFar) within the Institute of Physics of São Carlos – University of São Paulo, which is fully equipped to carry out both the experimental and computational components of the project. The research group belongs to the global network of laboratories accredited by Medicines for Malaria Venture (MMV) as a reference center forA malaria research. It also previously contributed to Brazil’s National Institutes of Science and Technology Program through the National Institute of Structural Biotechnology and Chemistry (INBEQMeDI). These affiliations underscore the group’s strong expertise in infectious diseases and the broader significance of the project in the global effort to combat parasitic diseases.

Drug-based Strategies
Product Development

Jun 2017 — May 2020

Brazil