title: Halogenated naphthochalcones and structurally related naphthopyrazolines with antitumor activity.
abstract: Three 3-(3-halo-4,5-dimethoxyphenyl)-1-(2-naphthyl)prop-2-en-1-ones 1 and three structurally related 2-pyrazolines 2 were prepared and assessed in vitro for anticancer activity. The chalcones 1 were antiproliferative with low double-digit micromolar IC50values against six tumor cell lines whereas the pyrazolines 2 showed low single-digit micromolar IC50values against this panel. The pyrazolines inhibited ATP-binding cassette efflux transporters of types P-gp and BCRP while the chalcones inhibited selectively BCRP. All test compounds induced an accumulation of HT-29 colon carcinoma cells in the G2/M phase of the cell cycle and they interfered with the microtubule and F-actin dynamics, but only the chalcones induced apoptosis in 518A2 melanoma cells after 24h.
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schmitt
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Draut
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany. Electronic address: Rainer.Schobert@uni-bayreuth.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006219:Halogens / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009281:Naphthalenes / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047188:Chalcones; D004273:DNA, Neoplasm; D006219:Halogens; D009281:Naphthalenes; D011720:Pyrazoles
keywords: BCRP; Chalcones; P-gp; Pyrazolines; TUNEL