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.
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. This tutorial shows a step-by-step procedure for anyone interested in designing and building chemical libraries with or without chemoinformatics experience. The aim is to explore various methodologies proposed by synthetic organic chemists and explore affordable chemical space using open-access chemoinformatics tools. As part of the tutorial, we discuss three examples of design: a Diversity-Oriented-Synthesis library based on lactams, a bis-heterocyclic combinatorial library, and a set of target-oriented molecules: isoindolinone based compounds as potential acetylcholinesterase inhibitors. This manuscript also seeks to contribute to the critical task of teaching and learning chemoinformatics.
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. Natural products such as peptides and macrocycles, and other compounds with unique features represent attractive sources to address complex diseases. Computational approaches that use chemoinformatics and molecular modeling methods contribute to speed up natural product-based drug discovery. Several research groups have recently used computational methodologies to organize data, interpret results, generate and test hypotheses, filter large chemical databases before the experimental screening, and design experiments. This review discusses a broad range of chemoinformatics applications to support natural product-based drug discovery. We emphasize profiling natural product data sets in terms of diversity; complexity; acid/base; absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties; and fragment analysis. Novel techniques for the visual representation of the chemical space are also discussed.
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 respons...
The chemical space of naturally occurring compounds is vast and diverse. Other than biologics, naturally occurring small molecules include a large variety of compounds covering natural products from different sources such as plant, marine, and fungi, to name a few, and several food chemicals. The systematic exploration of the chemical space of naturally occurring compounds have significant implications in many areas of research including but not limited to drug discovery, nutrition, bio- and chemical diversity analysis. The exploration of the coverage and diversity of the chemical space of compound databases can be carried out in different ways. The approach will largely depend on the criteria to define the chemical space that is commonly selected based on the goals of the study. This chapter discusses major compound databases of natural products and cheminformatics strategies that have been used to characterize the chemical space of natural products. Recent exemplary studies of the chemical space of natural products from different sources and their relationships with other compounds are also discussed. We also present novel chemical descriptors and data mining approaches that are emerging to characterize the chemical space of naturally occurring compounds.