Antonow, D., Jenkins, T.C., Howard, P.W. and Thurston, D.E. (2007) Synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione library: Effect of C2-aryl substitution on cytotoxicity and non-covalent DNA binding. Bioorganic & Medicinal Chemistry Letters, 15 (8). pp. 3041-3053. 10.1016/j.bmc.2007.01.054.
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A 23-member C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (PBD dilactam) library has been synthesized using Suzuki coupling, and the effect of base upon racemisation at the C11a-position during the cross-coupling reaction studied. Three library members (21, 30 and 33) were sufficiently cytotoxic in the NCI's preliminary screen to warrant further evaluation, and one (30, R = p-Br) was found to be cytotoxic at the sub-micromolar level in the A498 renal cancer cell line. DNA thermal denaturation studies suggested that this activity may be associated with non-covalent DNA interaction, and also demonstrated that introductin of C2-C3 unsaturation and addition of C2-aryl functionalities to the PBD dilactam skeleton significantly enhanced helix stabilisation compared to the unsubstituted PBD dilactam (6).
|Uncontrolled Keywords:||Antitumour agents; Dilactams; PBD; Racemisation; Suzuki coupling|
|Departments, units and centres:||Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry|
|Journal or Publication Title:||Bioorganic & Medicinal Chemistry Letters|
|Deposited By:||Library Staff|
|Deposited On:||02 Mar 2012 17:54|
|Last Modified:||02 Mar 2012 17:54|
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