Review
Biochemistry & Molecular Biology
Alejandro Gomez-Garcia, Jose L. Medina-Franco
Summary: This article reviews the progress in developing compound databases of natural origin, with a focus on chemoinformatic approaches. It also surveys the present state of developing Latin American NP databases and their practical applications in drug discovery.
Article
Biochemistry & Molecular Biology
Oscar Salvador Barrera-Vazquez, Juan Carlos Gomez-Verjan, Gil Alfonso Magos-Guerrero
Summary: Cellular senescence is a condition that involves significant changes in gene expression and cell proliferation arrest. Recent studies have suggested that pharmacological elimination of senescent cells can delay, prevent, and improve adverse outcomes related to age. Through the use of chemoinformatic tools in natural product chemical databases, new senolytic compounds candidates were discovered.
Review
Pharmacology & Pharmacy
Fernanda Saldivar-Gonzalez, Jose L. Medina-Franco
Summary: This article reviews the current state of chemical space in drug design and discovery, discussing advances in efficient navigation and assessment of chemical space diversity, as well as highlighting recent methods for generating visual representations of chemical space.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Medicinal
Alejandro Gomez-Garcia, Daniel A. Acuna Jimenez, William J. Zamora, Haruna L. Barazorda-Ccahuana, Miguel A. Chavez-Fumagalli, Marilia Valli, Adriano D. Andricopulo, Vanderlan da S. Bolzani, Dionisio A. Olmedo, Pablo N. Solis, Marvin J. Nunez, Johny R. Rodriguez Perez, Hoover A. Valencia Sanchez, Hector F. Cortes Hernandez, Jose L. Medina-Franco
Summary: The Latin American Natural Products Database (LANaPDB) is a public compound collection that gathers chemical information of natural products from various databases in Latin America. The current version includes chemical structures from six countries, with terpenoids, phenylpropanoids, and alkaloids being the most abundant compounds. LANaPDB covers a wide chemical space and many compounds exhibit drug-like properties.
Article
Chemistry, Multidisciplinary
Georg Niggemeyer, Anastasia Knyazeva, Raphael Gasper, Dale Corkery, Pia Bodenbinder, Julian J. Holstein, Sonja Sievers, Yao-Wen Wu, Herbert Waldmann
Summary: Design and synthesis of pseudo-natural products through recombination of natural product fragments enables the discovery of novel biologically relevant chemical matter. In this study, the combination of this principle with macrocycle formation was described, leading to the efficient synthesis of 163 macrocyclic pseudo-natural products. Biological investigation revealed their potent inducers of autophagy-related processes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemical Research Methods
Ricardo M. M. Borges, Gabriela de Assis Ferreira, Mariana Martins Campos, Andrew Magno Teixeira, Fernanda das Neves Costa, Fernanda Oliveira Chagas
Summary: We developed a tool called DBsimilarity that organizes structure databases into similarity networks, making it easier for natural product chemists to visualize information. The tool converts SDF files into CSV files, calculates compound similarities, and constructs similarity networks in CSV format. Using DBsimilarity, several potential antibiotic compounds were identified in Ginkgo biloba compounds, along with other compounds worthy of further investigation.
PHYTOCHEMICAL ANALYSIS
(2023)
Review
Chemistry, Multidisciplinary
George Karageorgis, Daniel J. Foley, Luca Laraia, Susanne Brakmann, Herbert Waldmann
Summary: PNPs are compounds formed by combining NP fragments in unique ways, inheriting important biological characteristics of NPs while exhibiting unprecedented bioactivity. The importance of design principles, synthesis, and biological research on PNP scaffolds is emphasized. PNPs are considered as a human-driven branch of the evolution of natural product structure.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Nadia A. Rivero-Segura, Juan C. Gomez-Verjan
Summary: The COVID-19 pandemic has caused significant disruptions worldwide, prompting the search for effective treatments against the SARS-CoV-2 virus. Research has shown that natural products from Mexico could be a valuable resource for drug development, with compound cichoriin showing potential as a therapeutic tool.
Article
Environmental Sciences
Masami Ishido
Summary: Endocrine disruptors have been assessed for health risks using bioassays and chemoinformatics. Rat hyperactivity assays were used to screen and classify endocrine disruptors into hyperactivity-associated and hyperactivity-negative chemicals. Epidemiological studies have shown a correlation between hyperactivity-associated chemicals and attention deficit hyperactivity disorder (ADHD), suggesting that these chemicals may be a subfamily of hyperactivity-associated chemicals among endocrine disruptors.
Article
Chemistry, Multidisciplinary
Alice Capecchi, Jean-Louis Reymond
Summary: The study successfully classified the origin of most NPs based on their molecular structure, providing useful information for further exploration of biosynthetic genes of NPs.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Chemistry, Multidisciplinary
Annina Burhop, Sukdev Bag, Michael Grigalunas, Sophie Woitalla, Pia Bodenbinder, Lukas Brieger, Carsten Strohmann, Axel Pahl, Sonja Sievers, Herbert Waldmann
Summary: By combining fragments derived from natural products in new ways, a collection of pseudo-NPs known as indofulvins has been created. These compounds define a new chemotype of autophagy inhibitors targeting mitochondrial respiration, showing potential pharmacological properties.
Article
Chemistry, Medicinal
Oscar S. Barrera-Vazquez, Gil A. Magos-Guerrero, Juan L. Escobar-Ramirez, Juan C. Gomez-Verjan
Summary: Previous studies have found that natural compound quercetin and synthetic compound dasatinib can reduce senescent cells, inflammation, and frailty in humans. This study used computer programs and molecular fingerprinting to identify six natural molecules with potential senolytic activity. Further experimental validation is needed for these molecules' senolytic activity.
MEDICINAL CHEMISTRY
(2023)
Article
Mathematics
Krasimir Kanchev, Ognian Kassabov, Velichka Milousheva
Summary: This paper studies Lorentz surfaces in R-1(3) satisfying the condition H-2-K≠0, referred to as Lorentz surfaces of general type. By introducing special isotropic coordinates and showing that the key characteristics of these surfaces satisfy a natural equation, a fundamental theorem of Bonnet type for this class of surfaces is proven.
Article
Biochemistry & Molecular Biology
Peter Ertl
Summary: There are significant differences between substituents present in natural products and those found in synthetic molecules. Natural products have more complex structures with oxygen heteroatoms and stereocenters, while synthetic molecules have nitrogen, sulfur heteroatoms and aromatic rings.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kenneth Lopez-Perez, Edgar Lopez-Lopez, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: Visualization of chemical space is crucial in various aspects of chemistry, such as compound library design and exploring structure-property relationships. ChemMaps is a visualization methodology that approximates compound distribution in large datasets based on satellite compounds with a similar mapping. Extended similarity indices are proposed to identify relevant regions and reduce high-dimensional data in describing a library's chemical space.
Article
Biochemical Research Methods
Karina Pikalyova, Alexey Orlov, Arkadii Lin, Olga Tarasova, Marcou Gilles, Dragos Horvath, Vladimir Poroikov, Alexandre Varnek
Summary: A new methodology based on generative topographic mapping (GTM) was introduced for predicting the drug resistance of HIV strains. The approach combines high accuracy and interpretability, allowing for visualization and analysis of sequence space and treatment optimization. Several case studies demonstrate the practicality of this method.
Article
Chemistry, Medicinal
Yuliana Zabolotna, Dmitriy M. Volochnyuk, Sergey Ryabukhin, Kostiantyn Gavrylenko, Dragos Horvath, Olga Klimchuk, Oleksandr Oksiuta, Gilles Marcou, Alexandre Varnek
Summary: Most existing computational tools for de novo library design focus on generating, selecting, and combining structural motifs to form new library members. However, these approaches appear to be more theoretical and disconnected from reality due to the lack of a direct link between the chemical space of the retrosynthesized fragments and the pool of available reagents. This paper presents a new open-source toolkit called Synthons Interpreter (SynthI), which merges these two chemical spaces into a single synthons space.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Yuliana Zabolotna, Dmitriy M. Volochnyuk, Sergey V. Ryabukhin, Dragos Horvath, Konstantin S. Gavrilenko, Gilles Marcou, Yurii S. Moroz, Oleksandr Oksiuta, Alexandre Varnek
Summary: Efficient synthesis of desired compounds is crucial for chemical space exploration in drug discovery, which is influenced by both established synthetic protocols and the availability of corresponding building blocks (BBs). This study analyzes the chemical space of 400,000 purchasable BBs, examining their physicochemical properties and diversity to assess their coverage of medicinal chemistry needs. The analysis is based on a universal topographic map that visualizes libraries and their differences in coverage.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Zlata Boiarska, Helena Perez-Pena, Anne-Catherine Abel, Paola Marzullo, Beatriz Alvarez-Bernad, Francesca Bonato, Benedetta Santini, Dragos Horvath, Daniel Lucena-Agell, Francesca Vasile, Maurizio Sironi, J. Fernando Diaz, Andrea E. Prota, Stefano Pieraccini, Daniele Passarella
Summary: Maytansinoids, a potent class of tubulin binders with cytotoxic activity, have been limited in their application as cytotoxins and chemical probes due to the complexity of natural product chemistry. In this study, the synthesis of long-chain derivatives and maytansinoid conjugates was reported, confirming that bulky substituents do not affect their activity or binding mode. These results provide new opportunities for the design of maytansine-based probes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Polina Oleneva, Yuliana Zabolotna, Dragos Horvath, Gilles Marcou, Fanny Bonachera, Alexandre Varnek
Summary: The Chimiotheque Nationale (CN) was compared with ZINC and ChEMBL to analyze its screening and biologically relevant compounds, including chemical space coverage, physicochemical properties, and Bemis-Murcko scaffold populations. Over 5 K CN-unique scaffolds were identified. Generative Topographic Maps (GTMs) were generated to compare compound populations. Hierarchical GTM (<< zooming >>) was used to create an ensemble of maps at different resolutions, from global overview to individual structure mapping. These maps were added to the ChemSpace Atlas website. The analysis of synthetic accessibility showed that only 29.7% of CN compounds can be fully synthesized using commercially available building blocks.
MOLECULAR INFORMATICS
(2023)
Review
Biochemistry & Molecular Biology
Helena Perez-Pena, Anne-Catherine Abel, Maxim Shevelev, Andrea E. E. Prota, Stefano Pieraccini, Dragos Horvath
Summary: Microtubules are essential in cellular processes and have potential as targets for cancer and neurodegeneration research. However, current tubulin binders have limitations, making the discovery of safer and more efficient agents necessary. Computer-aided design techniques and accessible tubulin-ligand structures can aid in the selection and design of new tubulin-targeting agents.
Article
Chemistry, Medicinal
Giuseppe Lamanna, Pietro Delre, Gilles Marcou, Michele Saviano, Alexandre Varnek, Dragos Horvath, Giuseppe Felice Mangiatordi
Summary: This study introduces a new de novo design algorithm called GENERA that combines the capabilities of a deep-learning algorithm for automated drug-like analogue design, called DeLA-Drug, with a genetic algorithm for generating molecules with desired target-oriented properties. GENERA was applied to the angiotensin-converting enzyme 2 (ACE2) target, and its ability to de novo design promising candidates was assessed using docking programs PLANTS and GLIDE. The study demonstrates that GENERA can effectively perform multiobjective optimization and generate focused libraries with better scores compared to a starting set of known ACE-2 binders.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Regina Pikalyova, Yuliana Zabolotna, Dragos Horvath, Gilles Marcou, Alexandre Varnek
Summary: The development of DNA-encoded library (DEL) technology has brought new challenges to the analysis of chemical libraries. This study introduces the concept of chemical library space (CLS) and compares four representations obtained using generative topographic mapping. These encodings allow for effective comparison of libraries and fine-tuning of matching criteria. The proposed CLS can be used for efficient analysis and selection of chemical libraries.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Regina Pikalyova, Yuliana Zabolotna, Dragos Horvath, Gilles Marcou, Alexandre Varnek
Summary: In chemical library analysis, it can be beneficial to describe libraries as individual items rather than collections of compounds. This is especially true for large non-selectable compound mixtures like DNA-encoded libraries (DELs). The chemical library space (CLS) is useful for managing a portfolio of libraries, similar to how chemical space (CS) helps manage portfolios of molecules. Mapping the CLS on meta-GTMs allows for analysis beyond pairwise library comparison, facilitating the selection of the most suitable libraries for specific projects.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Julia Revillo Imbernon, Celien Jacquemard, Guillaume Bret, Gilles Marcou, Esther Kellenberger
Summary: The screening of fragment libraries is crucial in drug discovery, with the success depending on the quality and design of the library meeting specific research requirements. This study conducted an inventory of commercial fragment libraries and developed a methodology to classify any library based on its similarity, coverage, and structural features, leading to the creation of a model that considers fragment diversity and ease of interpretation.
RSC MEDICINAL CHEMISTRY
(2022)
