Chemoinformatic Approach: The Case of Natural Products of Panama

Chemoinformatic analysis was used to characterize a compound database of natural products from Panama and other reference collections. Data mining allowed to compare drug-likeness properties with public and commercial software and to achieve a statistical analysis of the physicochemical properties. Visualization of the chemical space in 3D indicates a high structural similarity. Molecular flexibility and complexity were evaluated using 2D descriptors, whereas the molecular scaffold was obtained using the Murcko method, and these showed few differences between the explored data set. In this chapter, we also present and discuss an example of the application of the chemoinformatic approach using the concept of modeling the activity landscape to study the structure-activity relationships (SARs) of compounds with activity against Plasmodium falciparum

Latin American databases of natural products: biodiversity and drug discovery against SARS-CoV2

In this study, we evaluated 3444 Latin American natural products using cheminformatic tools. We also characterized 196 compounds for the first time from the flora of El Salvador that were compared with the databases of secondary metabolites from Brazil, Mexico, and Panama, and 42 969 compounds (natural, semi-synthetic, synthetic) from different regions of the world. The overall analysis was performed using drug-likeness properties, molecular fingerprints of different designs, two parameters similarity, molecular scaffolds, and molecular complexity metrics. It was found that, in general, Salvadoran natural products have a large diversity based on fingerprints. Simultaneously, those belonging to Mexico and Panama present the greatest diversity of scaffolds compared to the other databases. This study provided evidence of the high structural complexity that Latin America's natural products have as a benchmark. The COVID-19 pandemic has had a negative effect on a global level. Thus, in the search for substances that may influence the coronavirus life cycle, the secondary metabolites from El Salvador and Panama were evaluated by docking against the endoribonuclease NSP-15, an enzyme involved in the SARS CoV-2 viral replication. We propose in this study three natural products as potential inhibitors of NSP-15

Design and Diversity Analysis of Chemical Libraries in Drug Discovery

Chemical libraries and compound data sets are among the main inputs to start the drug discovery process at universities, research institutes, and the pharmaceutical industry. The approach used in the design of compound libraries, the chemical information they possess, and the representation of structures, play a fundamental role in the development of studies: chemoinformatics, food informatics, in silico pharmacokinetics, computational toxicology, bioinformatics, and molecular modeling to generate computational hits that will continue the optimization process of drug candidates. The prospects for growth in drug discovery and development processes in chemical, biotechnological, and pharmaceutical companies began a few years ago by integrating computational tools with artificial intelligence methodologies. It is anticipated that it will increase the number of drugs approved by regulatory agencies shortly

Descubrimiento de compuestos bioactivos a través de bioprospección en Panamá

Dentro del marco del Proyecto colaborativo entre la Universidad de Kansas y CIFLORPAN de la Universidad de Panamá se llevó a cabo bioprospección en la flora panameña, aún no explorada, para el descubrimiento de nuevas moléculas bioactivas contra tuberculosis, cáncer, enfermedad de Alzheimer y parasitarias. Se establecieron tres parcelas de 0.1 ha en tres parques nacionales: Parque Nacional Chagras (PNCH), Parque Nacional General de División Omar Torrijos Herrera (PNGDOTH) y el Parque Nacional Sarigua (PNS). Se identificaron un total de 2537 registros, distribuidos en 1536 (PNC), 708 ((PNGDOTH) y 293 (PNS). Se identificaron un total de 176 especies, 230 géneros pertenecientes a 95 familias. Se seleccionaron 197 especies para la evaluación biológica de plantas por su potencial farmacéutico con base en la búsqueda en la Base de Datos NAPRALERT. Para tal fin, se prepararon 302 extractos destanificados y 400 extractos etanólicos. Dos plantas Licania kallunkiae y Otoba novogranatensis demostraron actividad antituberculosa contra cepas de Mycobacterium tuberculosis sensibles (37Rv) y multirresistentes (MDR), con IC50 70.00 %). En los ensayos de citotoxicidad contra tres líneas celulares cancerosas humanas (NCI-MCF-7, NCI-H-460 y NCI-SF- 268), las plantas Erythroxylum sp., Enterolobium schomburgkii, Otoba novogranatensis, Hymenea courbaril, Rollinia sp., Casearia carymbosa, Miconia argentea, Erytrina fusca, Rauwolfia littoralis, Vouarana guianensis, Virola sp., Garcinia madruno, Inga sapindoides, Casearia sp., y Castilla elastica fueron activas. La evaluación de la actividad inhibidora contra la enzima acetilcolinesterasa permitió identificar 25 plantas como inhibidores selectivos de la enzima acetilcolinesterasa: Garcinia madruno, Ziziphus mauritiana, Erythrina fusca, Blakea herrerae, Guapira costaricana, Hortia colombiana, Tetrochidium sp., Pithecellobium hymeneaifolium. Pteridophyta, Psychotria capitata, Matayba sp., Cordia bicolor, Casearia corymbosa, Hymenea courbaril, Attalea butyracea, Bellucia pentamera, Indigofera suffruticosa, Machaerium sp, Bursera tomentosa, Garcinia madruno, Alysicarpus vaginalis, Dioclea megacarpa y Talisia nervosa. Mientras que en el ensayo de inhibición de butirilcolinesterasa, 10 plantas resultaron ser más activas: Pachira acuatica, Licaria sp., Warszewiczia coccinea, Rauwolfia littoralis, Nectandra sp, Neptunia sp, Piper sancti-felicis, Chamaecrista sp, Dussia atropurpurea y Elaeagio nitidifolia. Se seleccionaron cuatro plantas para estudios aislamiento biodirigidos y su caracterización estructural: Morinda rojoc, Homalomena wendlandii, Licania kallunkie y Warszewiczia coccinea. Se aislaron en total 17 compuestos, 4 de ellos nuevos reportes a la literatura y 13 conocidos, pero aislados por primera vez de plantas panameña

A New Cytotoxic Friedelane Acid – Pluricostatic Acid – and Other Compounds from the Leaves of Marila pluricostata

Bioassay-guided fractionation of the dichloromethane extract of the leaves of Marila pluricostata led to the isolation of 2α,3β-dihydroxy-D:A-friedoolean-28-oic acid (pluricostatic acid), a new friedelane triterpenoid, (1), ten known triterpenoids and three sterols. Their chemical structures were elucidated through spectroscopic analysis. The less polar fractions, on GC/MS analysis and comparison with a MS library, resulted in the identification of twenty four sesquiterpenoids. The new triterpenoid acid 1 showed cytotoxicity against the MCF-7, H-460, and SF-268 human cancer cell lines with GI50 values from 1.2 to 3.3 μg/mL

Trends and challenges in chemoinformatics research in Latin America

Chemoinformatics is an independent inter-discipline with a broad impact in drug design and discovery, medicinal chemistry, biochemistry, analytical and organic chemistry, natural products, and several other areas in chemistry. Through collaborations, scientific exchanges, and participation in international research networks, Latin American scientists have contributed to the development of this subject. The aim of this perspective is to discuss the status and progress of the chemoinformatic discipline in Latin America. We team up to provide an author´s perspective on the topics that have been investigated and published over the past twelve years, collaborations between Latin America researchers and others worldwide, contributions to open-access chemoinformatic tools such as web servers, and educational-related resources and events, such as scientific conferences. We conclude that linking and fostering collaboration within each nation as well as among other Latin American nations and globally is made possible by open science and the democratization of science. We also outline strategic actions that can boost the development and practice of chemoinformatic in the region and enhance the interaction between Latin American countries and the rest of 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) have 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 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 LANaPD 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 the 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. LANaPD will be updated adding more compounds from each database plus the addition of databases from other Latin American countries. The database is freely available at https://github.com/alexgoga21/LaNaPDB

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 a recently 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