Design and synthesis of novel 3,4-disubstituted pyrazoles for nanomedicine applications against malignant gliomas

European Journal of Medicinal Chemistry
Mauro Comes FranchiniElena Strocchi

Abstract

A series of novel 3,4-disubstituted pyrazoles were synthesized. The cytotoxicity against U87MG glioma cell line have been investigated in vitro and three of these compounds showed promising inhibitory activity on cell growth with an IC50 lower than 90 microM. AutoDock molecular docking into type I TGF-beta receptor (TGF-beta-RI; PDB: 1py5) has been done for lead optimization of the mentioned compounds as potential TGF-beta-RI1 inhibitors. In particular, 3-aryl-4-amido pyrazole containing long omega-amino-aliphatic chain emerged as a good candidate for further optimization. Entrapment into targetable PEG-based micelles improved growth inhibition IC50 values up to 100 nM and this could lead to a novel drug delivery strategy for treating glioblastoma.

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Citations

Dec 29, 2012·International Journal of Nanomedicine·Erica LocatelliMauro Comes Franchini
Jun 7, 2013·Expert Opinion on Drug Discovery·Shivaputra A PatilDuane D Miller
Apr 16, 2016·European Journal of Medicinal Chemistry·G BertuzziM Comes Franchini
Feb 24, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sayed M Riyadh
Jul 12, 2011·Chemistry : a European Journal·Erica LocatelliMauro Comes Franchini
Jun 22, 2020·Mikrochimica Acta·Pallavi P ChaudhariYuh-Ling Chen
Feb 21, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Valentina RebuttiniMauro Comes Franchini
Feb 27, 2015·Organic Letters·Daniel C SchmittRobert E Kyne

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