title: Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles.
abstract: Respiratory syncytial virus (RSV) has been identified as a main cause of hospitalisation in infants and children. To date, the current therapeutic arsenal is limited to ribavirin and palivizumab with variable efficacy. In this work, starting from a number of in-house series of previously described anti-RSV agents based on the benzimidazole scaffold, with the aim at gaining a better understanding of the related chemical features involved in potency and safety profiles, we applied a computational study including two focussed comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results allowed us to derive useful suggestions for the design of derivatives and also to set up statistical models predicting the potency and selectivity index (SI = CC50/EC50) of any new analogue prior to synthesis. Accordingly, here, we discuss preliminary results obtained through the applied exhaustive QSAR analyses, leading to design and synthesise more effective anti-RSV agents.
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cichero
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Novelli
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tasso
authors.affiliation: b Department of Biomedical Sciences , University of Cagliari, Cittadella Universitaria , Monserrato , CA , Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Delogu
authors.affiliation: b Department of Biomedical Sciences , University of Cagliari, Cittadella Universitaria , Monserrato , CA , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.affiliation: a Department of Pharmacy , University of Genoa , Genoa , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D010253:Respirovirus Infections / Q000188:drug therapy*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; C031000:benzimidazole
keywords: 3D-QSAR; Benzimidazoles; CoMFA; CoMSIA; respiratory syncytial virus