AlzyFinder: A Machine-Learning-Driven Platform for Ligand-Based Virtual Screening and Network Pharmacology.

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, presents significant challenges in drug development due to its multifactorial nature and complex pathophysiology. The AlzyFinder Platform, introduced in this study, addresses these challenges by providing a comprehensive, free web-based tool for parallel ligand-based virtual screening and network pharmacology, specifically targeting over 85 key proteins implicated in AD. This innovative approach is designed to enhance the identification and analysis of potential multitarget ligands, thereby accelerating the development of effective therapeutic strategies against AD.

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.

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.

Art driven by visual representations of chemical space.

Science and art have been connected for centuries. With the development of new computational methods, new scientific disciplines have emerged, such as computational chemistry, and related fields, such as cheminformatics. Chemoinformatics is grounded on the chemical space concept: a multi-descriptor space in which chemical structures are described.

Chemoinformatics and artificial intelligence colloquium: progress and challenges in developing bioactive compounds.

We report the main conclusions of the first Chemoinformatics and Artificial Intelligence Colloquium, Mexico City, June 15-17, 2022. Fifteen lectures were presented during a virtual public event with speakers from industry, academia, and non-for-profit organizations. Twelve hundred and ninety students and academics from more than 60 countries.

Chemical Multiverse: An Expanded View of Chemical Space.

Technological advances and practical applications of the chemical space concept in drug discovery, natural product research, and other research areas have attracted the scientific community's attention. The large- and ultra-large chemical spaces are associated with the significant increase in the number of compounds that can potentially be made and exist and the increasing number of experimental and calculated descriptors, that are emerging that encode the molecular structure and/or property aspects of the molecules. Due to the importance and continued evolution of compound libraries, herein, we discuss definitions proposed in the literature for chemical space and emphasize the convenience, discussed in the literature to use complementary descriptors to obtain a comprehensive view of the chemical space of compound data sets.

Approaches for enhancing the analysis of chemical space for drug discovery.

Introduction: Chemical space is a general conceptual framework that addresses the diversity of molecules and it has various applications. Moreover, chemical space is a cornerstone of chemoinformatics. In response to the increase in the set of chemical compounds in databases, generators of chemical structures, and tools to calculate molecular descriptors, novel approaches to generate visual representations of chemical space are emerging and evolving.

Towards the De Novo Design of HIV-1 Protease Inhibitors Based on Natural Products.

Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected.

Chemoinformatics-based enumeration of chemical libraries: a tutorial.

Virtual compound libraries are increasingly being used in computer-assisted drug discovery applications and have led to numerous successful cases. This paper aims to examine the fundamental concepts of library design and describe how to enumerate virtual libraries using open source tools. To exemplify the enumeration of chemical libraries, we emphasize the use of pre-validated or reported reactions and accessible chemical reagents.

Cheminformatics to Characterize Pharmacologically Active Natural Products.

Natural products have a significant role in drug discovery. Natural products have distinctive chemical structures that have contributed to identifying and developing drugs for different therapeutic areas. Moreover, natural products are significant sources of inspiration or starting points to develop new therapeutic agents.

Computational-aided design of a library of lactams through a diversity-oriented synthesis strategy.

Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold.

Exploring the chemical space and the bioactivity profile of lactams: a chemoinformatic study.

Lactams are a class of compounds important for drug design, due to their great variety of potential therapeutic applications, spanning cancer, diabetes, and infectious diseases. So far, the biological profile and chemical diversity of lactams have not been characterized in a systematic and detailed manner. In this work, we report the chemoinformatic analysis of beta-, gamma-, delta- and epsilon-lactams present in databases of approved drugs, natural products, and bioactive compounds from the large public database ChEMBL.

BIOFACQUIM: A Mexican Compound Database of Natural Products.

Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives in place to construct and maintain compound databases that are representative of their diversity.

Bicyclic acetals: biological relevance, scaffold analysis, and applications in diversity-oriented synthesis.

Natural products (NPs) have been shown to be an extraordinary source of bioactive compounds and three-dimensional complex frameworks that can be useful to produce high-value molecular collections that are able to address "undruggable" and difficult therapeutic targets. Bicyclic acetals are particularly relevant for these purposes, given their key role in several biological interactions and the structural and stereochemical diversity that comes from the many possible ring combinations. To investigate this topological diversity, we have systematically characterized in a systematic and detailed manner fused, spiro and bridged bicyclic acetals in a large set of NPs, highlighting the great potential of bicyclic acetals in Diversity-Oriented Synthesis (DOS).

Chemical Space and Diversity of the NuBBE Database: A Chemoinformatic Characterization.

NuBBE is the first library of natural products of Brazilian biodiversity. It includes a large variety of classes of compounds and structural types of secondary metabolites of plants, fungi, insects, marine organisms, and bacteria. So far the chemical diversity and complexity of NuBBE have not been characterized in a systematic and detailed manner.

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.

Ivermectin as an inhibitor of cancer stem‑like cells.

The aim of the present study was to demonstrate that ivermectin preferentially inhibited cancer stem‑like cells (CSC) in breast cancer cells and downregulated the expression of 'stemness' genes. Computational searching of DrugBank, a database of approved drugs, was performed using the principles of two‑dimensional similarity searching; the chemical structure of salinomycin was used as a query. Growth inhibition of the breast cancer cell lin e MDA‑MB‑231 by ivermectin was investigated in the total cell population, in cell spheroids and in sorted cells that expressed cluster of differentiation (CD)44+/CD24‑.