Development of New Antimitotic Agents Related to Combretastatins and Phenstatins
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Synthesis and conformational analysis of macrocyclic dihydroxystilbenes linked between the para-para positions.
A new family of diphenylethanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. The two phenyl rings are linked between the para-phenolic positions through a 3-oxapentamethylene or hexamethylene chain. The key macrocyclization step was achieved in moderate yields by using an intramolecular McMurry pinacol coupling of linked aromatic dialdehydes, exc...
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Several prodrugs of the naturally occurring combretastatins have undergone extensive clinical evaluation as vascular targeting agents (VTAs). Their increased selectivity toward endothelial cells together with their innate ability to rapidly induce vascular shutdown and inhibit tumor growth at doses up to 10-fold less than the maximum tolerated dose led to the clinical evaluation of combretastat...
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Cardiac glycosides are potent inhibitors of cell division. They may be useful as antitumor agents if the antimitotic effect can be dissociated from their cardiotoxic effect. We studied congeners of cardiac glycosides to determine whether the saccharide or the genin portion of the molecule contributes to its antimitotic effect. The concentration of glycoside required to inhibit PHA-stimulated 3H...
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تاریخ انتشار 2009