Antiproliferative agents that interfere with the cell cycle at the G1-->S transition: further development and characterization of a small library of stilbene-derived compounds.
In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some representative compounds. After in-depth investigations, 3'-phenyl-[1,1';4',1'']terphenyl-4,3'',5''-triol showed the most interesting biological profile, as it interferes with cell-cycle progression at the G(1)-->S transition, acting on retinoblastoma phosphorylation and inducing cell differentiation.
Pizzirani
Daniela
D
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Roberti
Marinella
M
Cavalli
Andrea
A
Grimaudo
Stefania
S
Di Cristina
Antonietta
A
Pipitone
Rosaria Maria
RM
Gebbia
Nicola
N
Tolomeo
Manlio
M
Recanatini
Maurizio
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D010766:Phosphorylation; D012175:Retinoblastoma / Q000737:chemistry / Q000378:metabolism; D016196:S Phase / Q000187:drug effects* / Q000502:physiology; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D013267:Stilbenes