Latin American Natural Product Database (LANaPDB): An Update.

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.

The workshops on computational applications in secondary metabolite discovery (CAiSMD).

We report the outcomes of the second session of the free online open-access workshop "Computational Applications in Secondary Metabolite Discovery (CAiSMD) 2022" that took place from 09 to 11 March 2022. The first session was held from 08 to 10 March 2021 and drew the attention of many early career scientists from academia and industry. The 23 invited speakers of this year's workshop also came from academia and industry and 222 registered participants from five continents (Africa, Asia, Europe, South, and North America) took part in the workshop.

Visualizing and Analyzing the Chemical Space of Natural Product Databases for Drug Discovery.

Chemical space is a multidimensional descriptor space that encloses all possible molecules, and at least 1 x 10 organic substances with a molecular weight below 500 Da are thought to be potentially relevant for drug discovery. Natural products have been the primary source of the new pharmacological entities marketed during the past forty years and continue to be one of the most productive sources for the creation of innovative medications. Chemoinformatics-based computational tools accelerate the drug development process for natural products.

Chemoinformatic Characterization of NAPROC-13: A Database for Natural Product C NMR Dereplication.

Natural products (NPs) are secondary metabolites of natural origin with broad applications across various human activities, particularly the discovery of bioactive compounds. Structural elucidation of new NPs entails significant cost and effort. On the other hand, the dereplication of known compounds is crucial for the early exclusion of irrelevant compounds in contemporary pharmaceutical research.

Neglected Tropical Diseases: A Chemoinformatics Approach for the Use of Biodiversity in Anti-Trypanosomatid Drug Discovery.

The development of new treatments for neglected tropical diseases (NTDs) remains a major challenge in the 21st century. In most cases, the available drugs are obsolete and have limitations in terms of efficacy and safety. The situation becomes even more complex when considering the low number of new chemical entities (NCEs) currently in use in advanced clinical trials for most of these diseases.

De Novo Design of Inhibitors of DNA Methyltransferase 1: A Critical Comparison of Ligand- and Structure-Based Approaches.

Designing and developing inhibitors against the epigenetic target DNA methyltransferase (DNMT) is an attractive strategy in epigenetic drug discovery. DNMT1 is one of the epigenetic enzymes with significant clinical relevance. Structure-based de novo design is a drug discovery strategy that was used in combination with similarity searching to identify a novel DNMT inhibitor with a novel chemical scaffold and warrants further exploration.

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.

Synthesis, biosimulation and pharmacological evaluation of benzimidazole derivatives with antihypertensive multitarget effect.

In this study, we synthesized a series of seven benzimidazole derivatives incorporating the structural acidic framework of angiotensin II (Ang II) type 1 receptor (ATR) antagonists (ARA-II) employing a three-step reaction sequence. The chemical structures were confirmed by H NMR, C NMR and mass spectral data. Through biosimulation, compounds 1-7 were identified as computational safe hits, thus, best candidates underwent ex vivo testing against two distinct mechanisms implicated in hypertension: antagonism of the Ang II type 1 receptor and the blockade of calcium channel.

Putative mechanism of a multivitamin treatment against insulin resistance.

Insulin resistance is caused by the abnormal secretion of proinflammatory cytokines in adipose tissue, which is induced by an increase in lipid accumulation in adipocytes, hepatocytes, and myocytes. The inflammatory pathway involves multiple targets such as nuclear factor kappa B, inhibitor of nuclear factor κ-B kinase, and mitogen-activated protein kinase. Vitamins are micronutrients with anti-inflammatory activities that have unclear mechanisms.

Food Chemicals and Epigenetic Targets: An Epi Food Chemical Database.

There is increasing awareness of epigenetics's importance in understanding disease etiologies and developing novel therapeutics. An increasing number of publications in the past few years reflect the renewed interest in epigenetic processes and their relationship with food chemicals. However, there needs to be a recent study that accounts for the most recent advances in the area by associating the chemical structures of food and natural product components with their biological activity.

Targeting Mannosyl-oligosaccharide glucosidase with natural products: potential pH-dependent inhibition explored through computer-aided drug design.

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBE, Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite's N-glycan biosynthesis.

BIOMX-DB: A web application for the BIOFACQUIM natural product database.

Natural product databases are an integral part of chemoinformatics and computer-aided drug design. Despite their pivotal role, a distinct scarcity of projects in Latin America, particularly in Mexico, provides accessible tools of this nature. Herein, we introduce BIOMX-DB, an open and freely accessible web-based database designed to address this gap.

Toward structure-multiple activity relationships (SMARts) using computational approaches: A polypharmacological perspective.

In the current era of biological big data, which are rapidly populating the biological chemical space, in silico polypharmacology drug design approaches help to decode structure-multiple activity relationships (SMARts). Current computational methods can predict or categorize multiple properties simultaneously, which aids the generation, identification, curation, prioritization, optimization, and repurposing of molecules. Computational methods have generated opportunities and challenges in medicinal chemistry, pharmacology, food chemistry, toxicology, bioinformatics, and chemoinformatics.

Consensus Pharmacophore Strategy For Identifying Novel SARS-Cov-2 M Inhibitors from Large Chemical Libraries.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (M) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. M is a target for anti-SARS-CoV-2 drug development, and multiple M crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an M consensus pharmacophore as a tool to expand the search for inhibitors.

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.

SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds.

Chemical Multiverse and Diversity of Food Chemicals.

Food chemicals have a fundamental role in our lives, with an extended impact on nutrition, disease prevention, and marked economic implications in the food industry. The number of food chemical compounds in public databases has substantially increased in the past few years, which can be characterized using chemoinformatics approaches. We and other groups explored public food chemical libraries containing up to 26,500 compounds.

The pursuit of accurate predictive models of the bioactivity of small molecules.

Property prediction is a key interest in chemistry. For several decades there has been a continued and incremental development of mathematical models to predict properties. As more data is generated and accumulated, there seems to be more areas of opportunity to develop models with increased accuracy.

Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules.

Virtual small molecule libraries are valuable resources for identifying bioactive compounds in virtual screening campaigns and improving the quality of libraries in terms of physicochemical properties, complexity, and structural diversity. In this context, the computational-aided design of libraries focused against antidiabetic targets can provide novel alternatives for treating type II diabetes mellitus (T2DM). In this work, we integrated the information generated to date on compounds with antidiabetic activity, advances in computational methods, and knowledge of chemical transformations available in the literature to design multi-target compound libraries focused on T2DM.

Anthocyanins: Molecular Aspects on Their Neuroprotective Activity.

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB).

Challenges in natural product-based drug discovery assisted with -based methods.

The application of traditional medicine by humans for the treatment of ailments as well as improving the quality of life far outdates recorded history. To date, a significant percentage of humans, especially those living in developing/underprivileged communities still rely on traditional medicine for primary healthcare needs. -based methods have been shown to play a pivotal role in modern pharmaceutical drug discovery processes.

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.