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Issue 16, 2012
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Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

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Abstract

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu2(glygly)2(ppz)(H2O)4]·2H2O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ∼12.5 μM, in addition to its excellent SOD mimics (IC50 ∼ 0.086 μM).

Graphical abstract: Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

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Supplementary files

Article information


Submitted
27 Oct 2011
Accepted
13 Feb 2012
First published
09 Mar 2012

Dalton Trans., 2012,41, 4955-4964
Article type
Paper

Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

S. Tabassum, W. M. Al-Asbahy, Mohd. Afzal, F. Arjmand and V. Bagchi, Dalton Trans., 2012, 41, 4955
DOI: 10.1039/C2DT12044E

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