A combined experimental and theoretical investigation of ruthenium(II)-hydrazone complex with DNA: Spectroscopic, nuclease activity, topoisomerase inhibition and molecular docking

摘要

A new Dichlorotetra(4-hydroxy-N'-(pyridin-4-ylmethylene)benzohydrazone)Ru(II) complex 1 has been synthesized and characterized using spectroscopic techniques. The structure of complex I has been optimized through ORCA computational programme package using B3LYP functionals. The complex binds efficiently with calf thymus DNA (CT-DNA) as monitored by UV-visible titrations (K-b = 4.8 x 10(5)), ethidium bromide displacement studies (K-sv = 1.39) as well as Circular Dichroism (CD) titrations. The complex intercalates with DNA base pairs. It shows cleavage of supercoiled (SC) DNA into nicked circular (NC) DNA efficiently via oxidative pathway. Complex 1 also inhibits Topoisomerase I (Topo I) relaxation activity at concentration 20 mu M. The molecular docking studies support that Topo I inhibition occur via blocking religation of G11 hydroxyl group. (C) 2018 Elsevier B.V. All rights reserved.