Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors

Abstract

The derivatives of 9-aminoacridine are generally inhibiting DNA Topoisomerase II (topo II), because of the ability of acridine nucleus to intercalate into DNA base pair. In the present study, an attempt is made to identify potent ligands from heterocyclic substituted 9-anilinoacridines which target against Topoisomerase II (1ZXM) by molecular modelling and docking studies using Schrodinger suite-2011 Maestro 9.2 version. The binding affinity of the designed compounds towards Topoisomerase II (1ZXM) was calculated based on the GLIDE score due to various interactions. Many of the designed compounds have good Glide score due to strong hydrogen bonding interactions, hydrophobic interactions and other parameters.. The N-Phenyl pyrazole substituted 9-anilino acridine derivatives 1a- 1x have good binding affinity with topo II with Glide score in the range of -5.58 to -7.78 when compared with the standard ledacrine (-5.24). The in silico ADMET screening of these compounds also performed by qikprop module of Schrodinger suite and the values of all the properties are within the recommended values. So it is worthwhile to synthesis the designed compounds for their antibacterial and cytotoxic activities against Topoisomerase II.