RESUMO
An analysis of the chemical environment of the oxygen atoms in the DNP database compared to the CMC and SCD databases was performed. Some structural clusters were identified which are predominant among the natural products and can be considered as distinctive features of NPs. Fifty-three oxygen-containing structural fragments that are distinctive for the DNP (distinctive set of fragments DSF) in comparison with the SCD have been identified. A new descriptor Mc was introduced for describing the ratio of atoms involved in the DSF to the total number of heavy atoms. A significant difference in the Mc values among the reference databases allowed the use of a specific cluster of the DSF as a tool for performing similarity searches for oxygen-containing NP molecules, or for evaluation or comparison of databases according to their NP-likeness. An example illustrating that the suggested approach could allow not only estimating the NP-likeness, but also serve as a tool for designing new NP-like compounds is provided. The suggested approach for NP-likeness evaluation moves away from the traditional ideas of scaffolds, cycles, linkers and substituents.
Assuntos
Produtos Biológicos/química , Bases de Dados Factuais , Desenho de Fármacos , Oxigênio/química , Algoritmos , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The analysis of known drugs (Comprehensive Medicinal Chemistry database (2008 version): http://www.mdl.com/products/knowledge/medicinal_chem/index.jsp ) and natural products (Koch et al., Proc Natl Acad Sci USA 102:17272-17277, 2008) has led to the identification of privileged saturated and aromatic heterocyclic ring pairs that we have termed as "BioCores." This article explains how the BioCores can be used for the design of novel lead-like scaffolds.
