Updating and profiling the natural product-likeness of Latin American compound libraries.

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

Navigating the Chemical Space and Chemical Multiverse of a Unified Latin American Natural Product Database: LANaPDB.

The number of databases of natural products (NPs) has increased substantially. Latin America is extraordinarily rich in biodiversity, enabling the identification of novel NPs, which has encouraged both the development of databases and the implementation of those that are being created or are under development. In a collective effort from several Latin American countries, herein we introduce the first version of the Latin American Natural Products Database (LANaPDB), a public compound collection that gathers the chemical information of NPs contained in diverse databases from this geographical region. The current version of LANaPDB unifies the information from six countries and contains 12,959 chemical structures. The structural classification showed that the most abundant compounds are the terpenoids (63.2%), phenylpropanoids (18%) and alkaloids (11.8%). From the analysis of the distribution of properties of pharmaceutical interest, it was observed that many LANaPDB compounds satisfy some drug-like rules of thumb for physicochemical properties. The concept of the chemical multiverse was employed to generate multiple chemical spaces from two different fingerprints and two dimensionality reduction techniques. Comparing LANaPDB with FDA-approved drugs and the major open-access repository of NPs, COCONUT, it was concluded that the chemical space covered by LANaPDB completely overlaps with COCONUT and, in some regions, with FDA-approved drugs. LANaPDB will be updated, adding more compounds from each database, plus the addition of databases from other Latin American countries.

Progress and Impact of Latin American Natural Product Databases.

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.

Inhibitors of DNA Methyltransferases From Natural Sources: A Computational Perspective.

Naturally occurring small molecules include a large variety of natural products from different sources that have confirmed activity against epigenetic targets. In this work we review chemoinformatic, molecular modeling, and other computational approaches that have been used to uncover natural products as inhibitors of DNA methyltransferases, a major family of epigenetic targets with therapeutic interest. Examples of computational approaches surveyed in this work are docking, similarity-based virtual screening, and pharmacophore modeling. It is also discussed the chemoinformatic-guided exploration of the chemical space of naturally occurring compounds as epigenetic modulators which may have significant implications in epigenetic drug discovery and nutriepigenetics.

[Polypharmacy prevalence and potentially inappropriate drug prescription in the elderly hospitalized for cardiovascular disease]. / Prevalencia de la polifarmacia y la prescripción de medicamentos inapropiados en el adulto mayor hospitalizado por enfermedades cardiovasculares.

INTRODUCTION: Many older adults have multiple medical conditions that require medical attention, exposing them to polypharmacy and to a higher increase in prescribing potentially inappropriate medications. These situations may cause adverse drug reactions, longer hospital stays, and death. The prevalence of polypharmacy in our country is estimated at 55% and inappropriate prescribing of medications of 30%. OBJECTIVE: To determine the prevalence of polypharmacy and potentially inappropriate drug prescription in older patients hospitalized for cardiovascular diseases. MATERIAL AND METHODS: Patients older than 70 years from a tertiary level hospital admitted to cardiology and angiology were included, from the period 2013-2014. Fragility status, polypharmacy, and drug prescription based on the Beer's criteria were established. The results were analyzed using descriptive statistics. For inferential analysis, cross tabulations with Pearson χ2 were used. RESULTS: 446 patients where included, with female predominance of 56% (mean age 76.6 ± 5.9 years). The prevalence of fragility was 35.7%, polypharmacy 84.5%, and inappropriate prescription of drugs 48.9%. Coefficient correlation between inappropriate prescription of drugs and polypharmacy was p = 0.001. CONCLUSIONS: The prevalence of polypharmacy and inappropriate prescription of drugs was higher than reported previously, which shows the situational diagnosis in this tertiary level hospital, considering a population with high cardiovascular risk.