title: Pt(II) complexes of a combretastatin A-4 analogous chalcone: effects of conjugation on cytotoxicity, tumor specificity, and long-term tumor growth suppression.
abstract: Three dichlorido(6-aminomethylnicotinate)platinum complexes 6 comprising a combretastatin A-4 analogous chalcone were tested on a panel of 21 tumor cell lines from 9 entities. Parent chalcone 1a and the directly linked conjugate 6a exhibited excellent antiproliferative activities, similar in magnitude [average log(IC(50)) values of -7.3 (1a) and -7.0 (6a)] and cell line specificity but slightly different in the mechanism of apoptosis induction. While 1a and 6a caused an equally fast rise in caspase-9 in the tested cancer cell lines, the downstream effector caspase-3 built up faster in cells treated with 1a compared to 6a, yet reached an equal end level. They also had different long-term effects on the regrowth of cancer cells treated with a single dose. In contrast, conjugates 6b,c featuring longer spacers between the Pt complex and the chalcone moieties were less antiproliferative than 6a.
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitatsstrasse 30, 95440 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
authors.forename: Andrea
authors.initials: A
authors.lastname: Dietrich
authors.forename: Sebastian
authors.initials: S
authors.lastname: Knauer
authors.forename: Miroslava
authors.initials: M
authors.lastname: Zoldakova
authors.forename: Angelika
authors.initials: A
authors.lastname: Fruehauf
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D013267:Stilbenes; D010984:Platinum; C058728:fosbretabulin