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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Authors: | Tabassum Sartaj Al-Asbahy Waddhaah M Afzal Mohd Arjmand Farukh Bagchi Vivek |
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Institution: | Department of Chemistry, Aligarh Muslim University, Aligarh 202201, UP, India. tsartaj62@yahoo.com |
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Abstract: | To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (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 (IC(50)~0.086 μM). |
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