Synthesis and evaluation of influenza A viral neuraminidase candidate inhibitors based on a bicyclo[3.1.0]hexane scaffold
Articolo
Data di Pubblicazione:
2016
Citazione:
Synthesis and evaluation of influenza A viral neuraminidase candidate inhibitors based on a bicyclo[3.1.0]hexane scaffold / C. Colombo, B..M. Pinto, A. Bernardi, A.J. Bennet. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 14:27(2016 Jul), pp. 6539-6553. [10.1039/C6OB00999A]
Abstract:
This manuscript describes a novel class of derivatives based on a bicyclo[3.1.0]hexane scaffold, proposed as mimics of sialic acid in a distorted boat conformation that is on the catalytic pathway of neuraminidases (sialidases). A general synthetic route for these constrained-ring molecules was developed using a photochemical reaction followed by a Johnson-Corey-Chaykovsky cyclopropanation. Functionalization with the goal of occupying the 150-cavity was also exploited. Inhibition assays demonstrated low micromolar inhibition against both group-1 (H5N1) and group-2 (H9N2) influenza neuraminidase subtypes, indicating good affinity for the alpha and beta sialic acid mimics and 150-cavity-targeted derivatives. These results provide a validation of a bicyclo[3.1.0]hexane scaffold as a mimic of a distorted sialic acid bound in the neuraminidase active site during catalysis.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
C. Colombo, B..M. Pinto, A. Bernardi, A.J. Bennet
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