Abstract:
:Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Brullo C,Rapetti F,Alfei S,Maric I,Rizzelli F,Mapelli M,Rosano C,Viale M,Bruno Odoi
10.1002/cmdc.202000122subject
Has Abstractpub_date
2020-06-04 00:00:00pages
961-969issue
11eissn
1860-7179issn
1860-7187journal_volume
15pub_type
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