Journal ArticleDOI
Properties and Architecture of Drugs and Natural Products Revisited
TLDR
This study demonstrates that computational chemical biology can assist in finding suitable molecular entities in collections of natural products for drug discovery and provides a basis for the design of new natural product-derived compound libraries.Abstract:
Computer-based analysis revealed that natural products exhibit a remarkable structural diversity of molecular frameworks and scaffolds that could be systematically exploited for combinatorial synthesis. Natural products offer a rich pool of unique molecular frameworks that complement "drug space". They possess desirable druglike properties rendering them ideal starting points for molecular design considerations. This review provides an overview of chemotype diversity and molecular properties of collections of drugs and druglike molecules, pure natural products, and natural product- derived compounds. Compared to druglike molecules, pure natural products contain more oxygen atoms and chiral cen- ters, and have less aromatic atoms on average. Among the natural product library we identified more than one thousand scaffolds that were not contained in any other compound set analyzed. This outcome provides a basis for the design of new natural product-derived compound libraries. Our study demonstrates that computational chemical biology can assist in finding suitable molecular entities in collections of natural products for drug discovery.read more
Citations
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Journal ArticleDOI
Natural products in drug discovery.
TL;DR: Various screening approaches are being developed to improve the ease with which natural products can be used in drug discovery campaigns, and data mining and virtual screening techniques are also being applied to databases of natural products.
Journal ArticleDOI
Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules
TL;DR: Diversity-oriented synthesis (DOS) aims to generate structural diversity in an efficient manner through the screening of small-molecule libraries for the discovery of novel, biologically interesting small molecules.
Journal ArticleDOI
Physicochemical properties of antibacterial compounds: implications for drug discovery.
Rosemarie O’Shea,Heinz E. Moser +1 more
TL;DR: The analysis of Payne and co-workers illustrates the challenge of antibacterial drug discovery and suggests that multiple parameters contribute to the high attrition rate.
Journal ArticleDOI
The impact of natural products upon modern drug discovery
TL;DR: This work analyzes natural product leads in the Lipinski and parallel universe in terms of drug-like properties, and shows that they can be divided into two equal subsets that complies with the Rule of Five.
Journal ArticleDOI
Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions☆
TL;DR: The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands and is a strong contributor to NP Ro5 outliers.
References
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Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
Journal ArticleDOI
Marine natural products.
TL;DR: This review covers the literature published in 2014 for marine natural products, with 1116 citations referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms.
Journal ArticleDOI
Drug-like properties and the causes of poor solubility and poor permeability
TL;DR: There are currently about 10000 drug-like compounds, and true diversity does not exist in experimental combinatorial chemistry screening libraries because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates.
Journal ArticleDOI
Natural Products as Sources of New Drugs over the Period 1981−2002
TL;DR: From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well, and in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame.
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Natural Products as Sources of New Drugs over the Last 25 Years
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