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Understanding the biological function of natural products' scaffolds from databases for the design of active compounds for the treatment of infectious diseases

Grant number: 19/05967-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2019
Effective date (End): April 30, 2021
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Adriano Defini Andricopulo
Grantee:Marilia Valli
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Biodiversity provides exclusive chemical scaffolds for the design of active compounds and is the main source of drugs approved worldwide (67% are either a natural product, semi-synthetic derivative, macromolecule isolated from an organism or have a pharmacophore group inspired by natural products). Natural products are efficient models for medicinal chemistry because they comprise scaffolds and structural properties that were evolutionary chosen with the ability to interact or bind to protein targets. Cataloged molecular diversity plays a key role in the discovery, design and development of drugs. If the chemical information from the biodiversity is properly accessible, organized and cataloged it may be much more useful for the design of new active molecules. Data repositories have enormously contributed to studies in several scientific fields such as medicine, chemistry, biology, taxonomy, ecology and environmental areas, and are one of the most important tools for drug discovery.The first natural product library from Brazilian biodiversity (NuBBE Database) was originally created by our research group and has proven to be an important resource for several areas of studies. Currently, this database contains more than 2,000 compounds, freely accessible online (http://nubbe.iq.unesp.br/portal/nubbedb.html) providing valuable and integrative data such as chemical, spectral, biological, taxonomic, geographic and pharmacological information. This database is an important research tool for drug design, medicinal chemistry, molecular modeling and for a wide variety of computational studies. The design of drugs is mainly based on the knowledge of the mechanisms by which bioactive molecules interact with pharmacological targets. The structure-based drug design (SBDD) by means of molecular modeling is one of the most efficient strategies used to evaluate the interaction of active compounds and its biological target and improve pharmacodynamics. This is a useful method to identify crucial intermolecular interactions in the process of molecular recognition and for the selection of hits that bind or fit to the target protein binding cavity.The focus of this project is to use a computational molecular modeling approach to identify scaffolds and hits in the natural products from the NuBBE database in order to generate information for the design of new prototypes for the treatment of neglected diseases. Additionally, the project aims at continuing the ongoing expansion of NuBBE Database in order to catalog secondary metabolites already described from Brazilian biodiversity, so that Brazil can provide the most complete natural products database of the equatorial and tropical environments.