RESUMO
Natural products (NPs) are a rich source of structurally novel molecules, and the chemical space they encompass is far from being fully explored. Over history, NPs have represented a significant source of bioactive molecules and have served as a source of inspiration for developing many drugs on the market. On the other hand, computer-aided drug design (CADD) has contributed to drug discovery research, mitigating costs and time. In this sense, compound databases represent a fundamental element of CADD. This work reviews the progress toward developing compound databases of natural origin, and it surveys computational methods, emphasizing chemoinformatic approaches to profile natural product databases. Furthermore, it reviews the present state of the art in developing Latin American NP databases and their practical applications to the drug discovery area.
Assuntos
Produtos Biológicos , Produtos Biológicos/química , Bases de Dados Factuais , Desenho de Fármacos , Descoberta de Drogas , América LatinaRESUMO
Background: Natural product databases are important in drug discovery and other research areas. An analysis of its structural content, as well as functional group occurrence, provides a useful overview, as well as a means of comparison with related databases. BIOFACQUIM is an emerging database of natural products characterized and isolated in Mexico. Herein, we discuss the results of a first systematic functional group analysis and global diversity of an updated version of BIOFACQUIM. Methods: BIOFACQUIM was augmented through a literature search and data curation. A structural content analysis of the dataset was performed. This involved a functional group analysis with a novel algorithm to automatically identify all functional groups in a molecule and an assessment of the global diversity using consensus diversity plots. To this end, BIOFACQUIM was compared to two major and large databases: ChEMBL 25, and a herein assembled collection of natural products with 169,839 unique compounds. Results: The structural content analysis showed that 15.7% of compounds and 11.6% of scaffolds present in the current version of BIOFACQUIM have not been reported in the other large reference datasets. It also gave a diversity increase in terms of scaffolds and molecular fingerprints regarding the previous version of the dataset, as well as a higher similarity to the assembled collection of natural products than to ChEMBL 25, in terms of diversity and frequent functional groups. Conclusions: A total of 148 natural products were added to BIOFACQUIM, which meant a diversity increase in terms of scaffolds and fingerprints. Regardless of its relatively small size, there are a significant number of compounds and scaffolds that are not present in the reference datasets, showing that curated databases of natural products, such as BIOFACQUIM, can serve as a starting point to increase the biologically relevant chemical space.