Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1,3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2-p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis.

Synthesis, biological and in silico evaluation of pure nucleobase-containing spiro (Indane-Isoxazolidine) derivatives as potential inhibitors of MDM2-p53 interaction

Maiuolo L.;Algieri V.;Russo B.;Tallarida M. A.;Nardi M.;Di Gioia M. L.;De Nino A.
2019

Abstract

Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1,3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2-p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis.
Indane derivatives; Isoxazolidines; MDM2-p53 inhibition; Spirooxindoles; A549 Cells; Humans; Microwaves; Molecular Structure; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53; Adenocarcinoma of Lung; Lung Neoplasms; Neuroblastoma; Spiro Compounds
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/298938
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