Molecular docking studies, in-silico ADMET screening, MM-GBSA binding free energy of some novel chalcone substituted 9-anilinoacridines as topoisomerase II inhibitors

Abstract

Novel chalcone substituted 9-anilinoacridines(1a-z) were designed by in-silico method for their Topoisomerase-II(Topo-II) inhibitory activity due to DNA-intercalating properties. Docking studies of compounds 1a-z as selective TOPO-II (id-1ZXM) inhibitors by using Schrodinger suit2016-2. Docking study for the molecules were performed by Glide module, in-silico ADMET screening by qikprop module and free binding energy by Prime-MMGBSA module. The binding affinity of molecules towards TOPO-II was selected on the basis of GLIDE score. Many compounds showed strong hydrophobic interactions and hydrogen bonding interactions to inhibit TOPO-II. The compounds 1a-z, except 1k have good binding affinity with Glide scores in the range of -5.52 to -7.27 when compared with the standard Ethacridine(-4.23). The ADMET properties are within the recommended values. MM-GBSA binding results of the most potent inhibitor are favourable. The compounds, 1x,z,m,f,r,i with significant Glide scores may produce significant anti-microbial and anti-cancer activities for further investigations may prove their therapeutic potential.