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.

Natural product (NP) databases are crucial tools in computer-aided drug design (CADD). Over the past decade, there has been a worldwide effort to assemble information regarding natural products (NPs) isolated and characterized in certain geographical regions. In 2023, it was published LANaPDB, and to our knowledge, this is the first attempt to gather and standardize all the NP databases of Latin America. Herein, we present and analyze in detail the contents of an updated version of LANaPDB, which includes 619 newly added compounds from Colombia, Costa Rica, and Mexico. The present version of LANaPDB has a total of 13 578 compounds, coming from ten databases of seven Latin American countries. A chemoinformatic characterization of LANaPDB was carried out, which includes the structural classification of the compounds, calculation of six physicochemical properties of pharmaceutical interest, and visualization of the chemical space by employing and comparing two different fingerprints (MACCS keys (166-bit) and Morgan2 (2048-bit)). Furthermore, additional analyses were made, and valuable information not included in the first version of LANaPDB was added, which includes structural diversity, molecular complexity, synthetic feasibility, commercial availability, and reported and predicted biological activity. In addition, the LANaPDB compounds were cross-referenced to two of the largest public chemical compound databases annotated with biological activity: ChEMBL and PubChem.

Pyrolysis as a waste treatment method has gained relevance because it can generate higher value-added products in addition to reducing the environment’s secondary pollution. In this study, the catalytic pyrolysis of waste tires was evaluated using NiTiO₃ and CoTiO₃ ilmenites as catalysts and precursors of metal catalysts with the aim to produce an oil enriched in high-value hydrocarbons, such as benzene, toluene, a xylenes mixture, and products less-reported, such as p-cymene and p-cymenene. The experiments were performed in an analytical pyrolyzer coupled to GC/MS. The effect of the nature of the catalysts on the product distribution was compared with the uncatalyzed reaction. The main products of uncatalyzed pyrolysis were D, L-limonene (~60%), and isoprene (~25%) due to the depolymerization of natural rubber. Meanwhile, Ni-ilmenites-based catalysts favored the formation of target compounds to expense D, L-limonene. Moreover, the presence of metal in reduced-ilmenite sharply enhanced the selectivity by ~50% concerning oxidized ilmenite and above 80% compared to the uncatalyzed reaction for p-cymene and p-cymenene. By contrast, the Co-ilmenites-based catalysts showed a marginal effect on secondary reactions. Finally, the feasibility of forming the aromatic terpenes, p-cymene, and p-cymenene from limonene in the non-catalytic pyrolysis was evaluated.

The aim of this research is to introduce the first curated natural product database from Colombia, Natural Products DataBase EjeCol (NPDBEjeCol), that has been made publicly available at www.npdbejecol.com. The compound library, compiled from the peer-reviewed literature, is composed of natural products derived from plants in the coffee region of Colombia. After extensive data standardization and curation, molecular descriptors of pharmaceutical relevance and molecular fingerprints of different designs were calculated in order to evaluate the structural diversity and explore their chemical space of compounds in NPDBEjeCol in comparison with natural products reference libraries. The current version of NPDBEjeCol contains 236 molecules, for which detailed information is available. This includes the compound name, linear notation, references to the peer-reviewed literature, CAS number, synonym names, and constitutional descriptors. Analysis of the drug-like properties suggest that NPDBEjeCol natural products are on average, compliant with the empirical Lipinski’s rule. Visualizations of the chemical space based on fingerprints uncovered one to three clusters of compounds and fragments. Among the phytochemical groups present in the database, terpenes are the most prominent, particularly those derived from monoterpenes and sesquiterpenes. NPDBEjeCol is the first Colombian natural products database of its kind in the country that can be publicly accessed through a web portal, facilitating open query, navigation, and visualization of the identified molecules.

Rubrolides are a family of naturally occurring 5-benzylidenebutenolides, which generally contain brominated phenol groups, and nearly half of them also present a chlorine attached to the butenolide core. Seven natural rubrolides were previously synthesized. When these compounds were tested against the model plant Raphanus sativus, six were found to exert a slight inhibition on plant growth. Aiming to exploit their scaffold as a model for the synthesis of new compounds targeting photosynthesis, nine new rubrolide analogues were prepared. The synthesis was accomplished in 2-4 steps with a 10-39% overall yield from 3,4-dichlorofuran-2(5H)-one. All compounds were evaluated for their ability to inhibit the whole Hill reaction or excluding photosystem I (PSI). Several natural rubrolides and their analogues displayed good inhibitory potential (IC₅₀ = 2-8 μM). Molecular docking studies on the photosystem II-light harvesting complex II (PSII-LHCII supercomplex) binding site were also performed. Overall, data support the use of rubrolides as a model for the development of new active principles targeting the photosynthetic electron transport chain to be used as herbicides.

Fragment libraries have a major significance in drug discovery due to their role in de novo design and enumerating large and ultra-large compound libraries. Although several fragment libraries are commercially available, most are derived from synthetic compounds. The number of fragment libraries derived from natural products is still being determined. Still, they represent a rich source of building blocks to generate pseudo-natural products and bioactive synthetic compounds inspired by natural products. In this work, we generated and analyzed a fragment library of natural products from Colombia, a highly diverse geographical region where fragment libraries are yet to be reported. We also generated and reported fragment libraries of three novel natural product libraries and, as a reference, the most updated version of FDA-approved drugs. In line with the principles of open science, the fragment libraries developed in this study are freely available.