Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles

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 a...

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Main Authors: Elena Cichero, Michele Tonelli, Federica Novelli, Bruno Tasso, Ilenia Delogu, Roberta Loddo, Olga Bruno, Paola Fossa
Format: Article
Language:English
Published: Taylor & Francis Group 2017-01-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:http://dx.doi.org/10.1080/14756366.2016.1256881
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author Elena Cichero
Michele Tonelli
Federica Novelli
Bruno Tasso
Ilenia Delogu
Roberta Loddo
Olga Bruno
Paola Fossa
author_facet Elena Cichero
Michele Tonelli
Federica Novelli
Bruno Tasso
Ilenia Delogu
Roberta Loddo
Olga Bruno
Paola Fossa
author_sort Elena Cichero
collection DOAJ
description 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.
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spelling doaj.art-b53256895220496d9c24799ccee5a4eb2022-12-21T23:42:39ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742017-01-0132137540210.1080/14756366.2016.12568811256881Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profilesElena Cichero0Michele Tonelli1Federica Novelli2Bruno Tasso3Ilenia Delogu4Roberta Loddo5Olga Bruno6Paola Fossa7University of GenoaUniversity of GenoaUniversity of GenoaUniversity of GenoaUniversity of Cagliari, Cittadella UniversitariaUniversity of Cagliari, Cittadella UniversitariaUniversity of GenoaUniversity of GenoaRespiratory 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.http://dx.doi.org/10.1080/14756366.2016.1256881BenzimidazolesCoMFACoMSIArespiratory syncytial virus3D-QSAR
spellingShingle Elena Cichero
Michele Tonelli
Federica Novelli
Bruno Tasso
Ilenia Delogu
Roberta Loddo
Olga Bruno
Paola Fossa
Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
Journal of Enzyme Inhibition and Medicinal Chemistry
Benzimidazoles
CoMFA
CoMSIA
respiratory syncytial virus
3D-QSAR
title Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
title_full Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
title_fullStr Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
title_full_unstemmed Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
title_short Benzimidazole-based derivatives as privileged scaffold developed for the treatment of the RSV infection: a computational study exploring the potency and cytotoxicity profiles
title_sort benzimidazole based derivatives as privileged scaffold developed for the treatment of the rsv infection a computational study exploring the potency and cytotoxicity profiles
topic Benzimidazoles
CoMFA
CoMSIA
respiratory syncytial virus
3D-QSAR
url http://dx.doi.org/10.1080/14756366.2016.1256881
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