1ftd
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(New page: 200px<br /><applet load="1ftd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ftd, resolution 2.Å" /> '''5'-D(*CP*GP*CP*GP*AP*A...)
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Revision as of 22:12, 24 November 2007
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5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'-SYMMETRIC BIS-BENZIMIDAZOLE COMPLEX
Overview
The synthesis and evaluation of the novel head-to-head bisbenzimidazole, compound 2,2-bis[4'-(3' '-dimethylamino-1', '-propyloxy)phenyl]-5,5-bi-1H-benzimidazole is described. An X-ray, crystallographic study of a complex with the DNA dodecanucleotide sequence, d(CGCGAATTCGCG) shows the compound bound in the A/T minor groove region of, a B-DNA duplex and that the head-to-head bisbenzimidazole motif, hydrogen-bonds to the edges of all four consecutive A:T base pairs. The, compound showed potent growth inhibition with a mean IC(50) across an, ovarian carcinoma cell line panel of 0.31 microM, with no significant, cross-resistance in two acquired cisplatin-resistant cell lines and a low, level of cross-resistance in the P-glycoprotein overexpressing acquired, doxorubicin-resistant cell line. Studies with the hollow fiber assay and, in vivo tumor xenografts showed some evidence of antitumor activity.
About this Structure
1FTD is a Protein complex structure of sequences from [1] with MG and E97 as ligands. Full crystallographic information is available from OCA.
Reference
A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity., Mann J, Baron A, Opoku-Boahen Y, Johansson E, Parkinson G, Kelland LR, Neidle S, J Med Chem. 2001 Jan 18;44(2):138-44. PMID:11170623
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