CONSTRUCTION OF A DATABASE AND IDENTIFICATION OF CYANOBACTERIAL METABOLITES WITH POTENTIAL TO INHIBIT NEUTROPHIL ELASTASE

Ana Marcia de Almeida (1,2,3), (1,2) Angèlica Ribeiro Soares, Nelilma Correia Romeiro (1,2)

(1) Laboratório Integrado de Computação Científica – LICC, Universidade Federal do Rio de Janeiro, Campus Macaé, RJ.
(2) Grupo de Produtos Naturais de Organismos Aquáticos
(3) Programa de Pós-Graduação em Produtos Bioativos e Biociências (PPG-ProdBio), Universidade Federal do Rio de Janeiro, Campus Macaé, RJ..
[email protected]

Chronic Obstructive Pulmonary Disease (COPD) is characterized by non-fully reversible airflow limitation. There is a delicate imbalance between proteases and antiproteases. This imbalance may be due to neutrophil infiltration into the lung and protease release, such as Neutrophil Elastase (NE), targeting a number of molecules for COPD therapy (Lucas et al., 2013). It is worth noting that the available treatments have been shown to be incapable of reversing / improving the COPD process. With advances in genomic techniques, knowledge about biosynthetic enzymes in cyanobacteria has been growing, which has revealed a great biochemical potential for the obtention of bioactive substances and secondary metabolites of cyanobacteria are promising drug candidates.
In this context, the purpose of this work was to build a molecular database to provide information on various cyanobacteria and their metabolites, facilitating bioprospection in an innovative initiative. The 2D structures of cyanobacteria metabolites were obtained in scientific articles, stored in SMILES notation and standardized with Instant JChem. After this step the molecules were submitted to chemogenomics with PIDGIN software in order to identify potential inhibitors of Elastase, for further studies based on ligands (2D) and 3D structure.
The database of cyanobacteria metabolites under construction has 500 annotated molecules and references so far. Chemogenomics showed that 756 targets of the 1080 available from the PIDGIN software library had potential hits. Among these, 17 (seventeen) cyanobacterial metabolites had specific similarity with neutrophil elastase inhibitors described in CHEMBL database. For example, two promising molecules have been suggested by chemogenomics: Pompanopeptin A and Majusculamide C, which have been isolated from oscillatorium sp and Lyngbya sp, respectively. Finally, docking studies will be carried out with GOLD version 4.1.2. in order to deepen the in silico correlation between structure and activity (SAR) predicted by PIDGIN and to corroborate the predictions of the mechanism of action. Also, ADMET descriptors, such as Lipinski’s rule of five (Lipinski et al., 2001), among others, will be calculated with ChemAxon's ChemSketch software aiming at selecting substances to be assayed for neutrophil elastase inhibition.

References
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