Molecular docking, DFT and antimicrobial studies of Cu(II) complex as topoisomerase I inhibitor

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.