title: Predicting human serum albumin affinity of interleukin-8 (CXCL8) inhibitors by 3D-QSPR approach.
abstract: A novel class of 2-(R)-phenylpropionamides has been recently reported to inhibit in vitro and in vivo interleukin-8 (CXCL8)-induced biological activities. These CXCL8 inhibitors are derivatives of phenylpropionic nonsteroidal antiinflammatory drugs (NSAIDs), high-affinity ligands for site II of human serum albumin (HSA). Up to date, only a limited number of in silico models for the prediction of albumin protein binding are available. A three-dimensional quantitative structure-property relationship (3D-QSPR) approach was used to model the experimental affinity constant (K(i)) to plasma proteins of 37 structurally related molecules, using physicochemical and 3D-pharmacophoric descriptors. Molecular docking studies highlighted that training set molecules preferentially bind site II of HSA. The obtained model shows satisfactory statistical parameters both in fitting and predicting validation. External validation confirmed the statistical significance of the chemometric model, which is a powerful tool for the prediction of HSA binding in virtual libraries of structurally related compounds.
authors.affiliation: Molecular Discovery Ltd., 4, Chandos Street, W1A 3BQ, London, United Kingdom.
authors.forename: Loretta
authors.initials: L
authors.lastname: Aureli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
authors.forename: Maria Candida
authors.initials: MC
authors.lastname: Cesta
authors.forename: Roberto
authors.initials: R
authors.lastname: Anacardio
authors.forename: Lucio
authors.initials: L
authors.lastname: De Simone
authors.forename: Alessio
authors.initials: A
authors.lastname: Moriconi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008958:Models, Molecular; D010666:Phenylpropionates / Q000097:blood / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D010666:Phenylpropionates; D012709:Serum Albumin