Synthesis and antiproliferative activity of new derivatives containing the polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3',4':2,3]azepino[4,5-f]azocine

European Journal of Medicinal Chemistry
Benedetta MaggioGiuseppe Daidone

Abstract

The reaction under reflux between 1-phenyl-3-R-5-methylaminopyrazoles and 2,5-hexanedione lead to 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3',4':2,3]azepino[4,5-f]azocine derivatives 3b-g. These unusual molecules show the structural complexity of many biologically active natural products and are endowed with the chemical diversity that is required in drug discovery. The compounds 3b,e were reduced by hydrogen in the presence of Palladium on activated charcoal to give the dihydro derivatives 5b,e. Compounds 3b-f and 5b,e were selected by the NCI to evaluate their in vitro antiproliferative activity against 60 human cell lines derived from nine clinically isolated cancer types (leukaemia, lung, colon, melanoma, renal, ovarian, brain, breast, and prostate). The most active compound of this series, caused a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed that this compound favours pRb dephosphorylation.

References

Jun 1, 1994·Cancer Metastasis Reviews·P L Olive, R E Durand
Aug 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G ToffoliM Boiocchi
Mar 21, 2001·Human Molecular Genetics·J R Nevins

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Citations

May 20, 2015·Chemistry and Physics of Lipids·María Elisa MarianiGerardo Daniel Fidelio
Jul 4, 2016·European Journal of Medicinal Chemistry·Benedetta MaggioGiuseppe Daidone
Jul 31, 2016·European Journal of Medicinal Chemistry·Stella CascioferroGiuseppe Daidone
Mar 31, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eva Fischer-FodorNatalia Miklášová

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