title: Synthesis and evaluation of a series of resveratrol analogues as potent anti-cancer agents that target tubulin.
abstract: A series of novel diarylacrylonitrile andtrans-stilbene analogues of resveratrol has been synthesized and evaluated for their anticancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogues3band4aexhibited the most potent anticancer activity of all the analogues synthesized in this study, with GI50values of < 10 nM against almost all the cell lines in the human cancer cell panel. Compounds3band4awere also screened against the acute myeloid leukemia (AML) cell line, MV4-11, and were found to have potent cytotoxic properties that are likely mediated through inhibition of tubulin polymerization. Results from molecular docking studies indicate a common binding site for4aand3bon the 3,3-tubulin heterodimer, with a slightly more favorable binding for3bcompared to4a; this is consistent with the results from the microtubule assays, which demonstrate that4ais more potent than3bin inhibiting tubulin polymerization in MV4-11 cells. Taken together, these data suggest that diarylacrylonitriles3band4amay have potential as antitubulin therapeutics for treatment of both solid and hematological tumors.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Nikhil R
authors.initials: NR
authors.lastname: Madadi
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zong
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Ketkar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Narsimha R
authors.initials: NR
authors.lastname: Penthala
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Venumadhav
authors.initials: V
authors.lastname: Janganati
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Shobanbabu
authors.initials: S
authors.lastname: Bommagani
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Eoff
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Guzman
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks