Cover Picture: Tetrahydroisoquinolinone‐Based Steroidomimetic and Chimeric Microtubule Disruptors (ChemMedChem 1/2014). Issue 1 (January 2014)

• Record Type: Journal Article
• Authors: Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Dohle, Wolfgang; Hamel, Ernest; Ferrandis, Eric; Fiore, Ann; Kasprzyk, Philip G.; Potter, Barry V. L.
• Is Part Of: ChemMedChem. Volume 9:Issue 1(2014:Jan.)
• Page Start: 1
• Page End: 1
• Publication Date: 2014-01
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201390056
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>The front cover picture shows</bold> cultured HeLa cells expressing recombinant tetracysteine‐tagged tubulin and labelled with the green fluorescent biarsenical dye FlAsH (background). Cells were counterstained for DNA (blue) and imaged by confocal microscopy. In the foreground, the crystal structure of bovine alpha (brown) and beta (purple) tubulin attached to the rat framework protein stathmin 4 (white) is shown, with guanosine di‐ or tri‐phosphate (containing green atoms) and a colchicine derivative (containing pink atoms) bound (PDB: 1SA0). Using a translational SAR strategy, microtubule disruptors were designed based on the estrogen metabolite 2‐methoxyestradiol (left) and the natural product colchicine (right). Fusion of the AB‐ring system (red) of 2‐methoxyestradiol, sulfamoylated (yellow) for optimum pharmaceutical properties, with the trimethoxyaryl subpharmacophore (purple) of colchicine afforded a new and highly potent "chimeric" class of tetrahydroisoquinoline‐based anticancer agent (center). Tubulin image reproduced with permission from Thomas J. Deerinck (NCMIR/UC San Diego, USA). For more details, see the Full Paper by Barry V. L. Potter et al. on <ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">p. 85 ff.</ext-link><boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4t3pvpx0" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>