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J Chem Inf Model ; 53(2): 354-67, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23351040


Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance. In this study we have analyzed molecules from three distinct chemical spaces (i) approved drugs, (ii) human metabolites, and (iii) traditional Chinese medicine (TCM) to investigate four aspects determining the disposition of small organic molecules. First, we examined the physicochemical properties of these three classes of molecules and identified characteristic features resulting from their distinctive biological functions. For example, human metabolites and TCM molecules can be larger and more hydrophobic than drugs, which makes them less likely to cross membranes. We then quantified the shifts in physicochemical property space induced by metabolism from a holistic perspective by analyzing a data set of several thousand experimentally observed metabolic trees. Results show how the metabolic system aims to retain nutrients/micronutrients while facilitating a rapid elimination of xenobiotics. In the third part we compared these global shifts with the contributions made by individual metabolic reactions. For better resolution, all reactions were classified into phase I and phase II biotransformations. Interestingly, not all metabolic reactions lead to more hydrophilic molecules. We were able to identify biotransformations leading to an increase of logP by more than one log unit, which could be used for the design of drugs with enhanced efficacy. The study closes with the analysis of the physicochemical properties of metabolites found in the bile, faeces, and urine. Metabolites in the bile can be large and are often negatively charged. Molecules with molecular weight >500 Da are rarely found in the urine, and most of these large molecules are charged phase II conjugates.

Medicamentos de Ervas Chinesas/metabolismo , Metaboloma , Preparações Farmacêuticas/metabolismo , Bibliotecas de Moléculas Pequenas/metabolismo , Bile/metabolismo , Biotransformação , Bases de Dados de Produtos Farmacêuticos , Descoberta de Drogas , Medicamentos de Ervas Chinesas/química , Fezes/química , Humanos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/urina , Bibliotecas de Moléculas Pequenas/química
J Cheminform ; 3(1): 37, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-21999342


BACKGROUND: The Blue Obelisk movement was established in 2005 as a response to the lack of Open Data, Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistry research by promoting interoperability between chemistry software, encouraging cooperation between Open Source developers, and developing community resources and Open Standards. RESULTS: This contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveys progress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry. CONCLUSIONS: We show that the Blue Obelisk has been very successful in bringing together researchers and developers with common interests in ODOSOS, leading to development of many useful resources freely available to the chemistry community.