1. Molecular docking, DFT and antimicrobial studies of Cu(II) complex as topoisomerase I inhibitor.
- Author
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Parveen S, Arjmand F, Zhang Q, Ahmad M, Khan A, and Toupet L
- Subjects
- Copper, Escherichia coli, Molecular Docking Simulation, Staphylococcus aureus, Topoisomerase I Inhibitors pharmacology, Anti-Infective Agents, Antineoplastic Agents
- Abstract
Herein, we report the synthesis and single crystal X-ray structure of Cu(II)-picolinic acid complex, 1 as a potent topoisomerase I inhibitor. The complex 1 crystallized in the triclinic crystal system with space group P -1. Comparative in vitro binding studies of complex 1 with CT DNA and tRNA were carried out revealing an electrostatic binding mode with higher binding propensity towards tRNA. The intrinsic bonding constant value, K
b was calculated to be 4.36 × 104 and 8.78 × 104 M-1 with CT DNA and tRNA respectively. DNA cleavage activity was carried out with a pBR322 plasmid DNA substrate to ascertain the cleaving ability. Furthermore, Topo-I inhibition assay of complex 1 , performed via gel electrophoresis revealed a significant inhibitory effect on the enzyme catalytic activity at a minimum concentration of 15 µM. The DFT studies were carried out to provide better insight in the electronic transitions observed in the absorption spectrum of the complex 1 . Molecular docking studies were carried out with DNA, RNA and Topo-I to determine the specific binding preferences at the target site and complement the spectroscopic studies. The antimicrobial potential of complex 1 was screened against E. coli , S. aureus , P. aeruginosa , B. subtilis and C. albicans ; and compared with doxycycline, exhibiting an excellent maximum zone of inhibition of 28 mm against E. coli. Communicated by Ramaswamy H. Sarma.- Published
- 2021
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