title: Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells.
abstract: To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phase and also to induce differentiation in acute myelogenous leukemia HL60 cells. Compared to resveratrol, the synthetic terphenyl 13g showed a more potent apoptotic and differentiating activity. Moreover, it was active on both multidrug resistance and Bcr-Abl-expressing cells that were resistant to resveratrol.
authors: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. marinella.roberti@unibo.it
authors: Marinella
authors: M
authors: Roberti
authors: Daniela
authors: D
authors: Pizzirani
authors: Maurizio
authors: M
authors: Recanatini
authors: Daniele
authors: D
authors: Simoni
authors: Stefania
authors: S
authors: Grimaudo
authors: Antonietta
authors: A
authors: Di Cristina
authors: Vincenzo
authors: V
authors: Abbadessa
authors: Nicola
authors: N
authors: Gebbia
authors: Manlio
authors: M
authors: Tolomeo