QSAR model for predicting binding affinity to adenosine A2B receptors based on chromone scaffold

• Tipo: Artigo em Revista Científica Internacional
• Data: 2010

Autores

Virginia Rivero (Autor) Outra; Marta Teijeira (Autor) Outra; Fernanda Borges (Autor) FCUP; Alexandra Gaspar (Autor) FCUP; Miguel Angel Cabrera (Autor) Outra; Aliuska Morales Helguera (Autor) Outra

Revista

Título: Purinergic Signalling

Vol. 6 Nº 1

Páginas: 108-109

ISSN: 1573-9538

Editora: Springer Nature

Indexação

ISI Web of Science

Classificação Científica

FOS: Ciências da engenharia e tecnologias > Engenharia química

CORDIS: Ciências Físicas > Química > Química aplicada > Química farmacêutica ; Ciências Físicas > Química > Química estrutural

Outras Informações

Abstract (EN): A2B adenosine receptor (A2BAR) antagonists have been proposed as an attractive pharmacological tool for the treatment of several diseases, such as asthma, Alzheimer’s disease, cystic fibrosis and type II diabetes [1]. A wide variety of A2BAR antagonists can currently be found in the literature, specifically xanthine derivatives [2]; however, other chemicals, such as chromone structures, are little studied, and they could be new A2BAR ligands. In this work, our attention has been pointed out toward the evolution of the new quantitative structure–activity relationships (QSAR) model based on chromone structures to predict affinity for A2B ARs and using molecular descriptors derived from TOPS-MODE approach (http://www.modeslab.com). With the compilation of a dataset of chromones synthesized in our laboratories, or elsewhere, and testing their ability to displace [3H]-DPCPX from cloned human A2B adenosine, we recognized a unique opportunity to attempt to build a predictive QSAR model. The regression QSAR model is given below together with the regression statistical parameters: %I ¼
10:71 þ 7:88  10
7  m0mDip 11
1:05  10
2  m0mDip2 5 þ 0:203m1m AbPBH2 4 N ¼ 20 s ¼ 8:14 R2 ¼ 92:20 F ¼ 32:80 q2 LOO ¼ 89:17 p < 10
5 ThisQSAR model allowed us to carry out a fragment analysis of the set ofA2BAR antagonist to find the best structural features that allow the development of new potent antagonist. Substructural analysis also helped to understand the influence of the physicochemical properties on modulation of binding affinity at A2BAR subtype. This is the first study where a substructural analysis of A2BAR supports the design and selection of novel candidates structurally based on chromone scaffold.

Idioma: Português

Tipo (Avaliação Docente): Científica