Withdrawn: Variations in Altered Global Gene Expression caused by Topoisomerase II Poisons Assessed with Reference to Differences in DNA Binding.

Unlabelled: The article has been withdrawn at the request of the authors of the journal Current Molecular Pharmacology. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.

Characterisation of bis(4-aminoquinoline)s as α adrenoceptor allosteric modulators.

The development of sub-type selective α adrenoceptor ligands has been hampered by the high sequence similarity of the amino acids forming the orthosteric binding pocket of the three α adrenoceptor subtypes, along with other biogenic amine receptors. One possible approach to overcome this issue is to target allosteric sites on the α adrenoceptors. Previous docking studies suggested that one of the quinoline moieties of a bis(4-aminoquinoline), comprising a 9-carbon methylene linker attached via the amine groups, could interact with residues outside of the orthosteric binding site while, simultaneously, the other quinoline moiety bound within the orthosteric site.

Molecular dynamic simulations of diacridine binding to DNA: Indications that C6 diacridine can bisintercalate spanning two base pairs.

Dimers of 9-aminoacridine linked via the 9-amino group with polymethylene chains, termed diacridines, are known to bisintercalate into DNA when the linker comprises 6 or more methylene units. There are no literature reports of crystal or NMR solution structures for bisintercalated diacridine-DNA complexes, and the issue of the structure of the C6 ([CH ] linker where n = 6) diacridine complex remains unresolved. Previously, based on simple geometric considerations, it was proposed that C6 diacridine could only span a single base pair, which requires that its bifunctional reaction violates the widely-observed "neighbor exclusion principle" where bound intercalators are separated by at least 2 base pairs.

Structures and dynamics of DNA complexes of the desmethyl analog of the cytotoxin MLN944: Insights into activity when a methyl isn't futile.

Structure activity relationships for tricyclic-carboxamide topoisomerase II poisons indicate that cytotoxicity is enhanced by the presence of methyl, and other, groups in the position peri to the carboxamide. Linked dimers of phenazine-1-carboxamides are potent cytotoxins and one phenazine dimer, MLN944 (alternatively XR5944), has been in clinical trial. MLN944 is a template inhibitor of transcription, whereas corresponding monomers are not.

Homobivalent Conjugation Increases the Allosteric Effect of 9-aminoacridine at the α1-Adrenergic Receptors.

The α-adrenergic receptors are targets for a number of cardiovascular and central nervous system conditions, but the current drugs for these receptors lack specificity to be of optimal clinical value. Allosteric modulators offer an alternative mechanism of action to traditional α-adrenergic ligands, yet there is little information describing this drug class at the α-adrenergic receptors. We have identified a series of 9-aminoacridine compounds that demonstrate allosteric modulation of the α- and α-adrenergic receptors.