Synthesis and evaluation of spiroisoxazoline oxindoles as anticancer agents
Bioorganic & medicinal chemistry, 2014•Elsevier
Restoring p53 levels through disruption of p53–MDM2 interaction has been proved to be a
valuable approach in fighting cancer. We herein report the synthesis and evaluation of
eighteen spiroisoxazoline oxindoles derivatives as p53–MDM2 interaction inhibitors. Seven
compounds showed an antiproliferative profile superior to the p53–MDM2 interaction
inhibitor nutlin-3, and induced cell death by apoptosis. Moreover, proof-of-concept was
demonstrated by inhibition of the interaction between p53 and MDM2 in a live-cell …
valuable approach in fighting cancer. We herein report the synthesis and evaluation of
eighteen spiroisoxazoline oxindoles derivatives as p53–MDM2 interaction inhibitors. Seven
compounds showed an antiproliferative profile superior to the p53–MDM2 interaction
inhibitor nutlin-3, and induced cell death by apoptosis. Moreover, proof-of-concept was
demonstrated by inhibition of the interaction between p53 and MDM2 in a live-cell …
Abstract
Restoring p53 levels through disruption of p53–MDM2 interaction has been proved to be a valuable approach in fighting cancer. We herein report the synthesis and evaluation of eighteen spiroisoxazoline oxindoles derivatives as p53–MDM2 interaction inhibitors. Seven compounds showed an antiproliferative profile superior to the p53–MDM2 interaction inhibitor nutlin-3, and induced cell death by apoptosis. Moreover, proof-of-concept was demonstrated by inhibition of the interaction between p53 and MDM2 in a live-cell bimolecular fluorescence complementation assay.
Elsevier