No abstract

The 2D structures of compounds were built and converted into 3D using vLife MDS 3.0 software. The 3D structures were then energetically minimized up to the rms gradient of 0.01 using the CHARMM22 force field. All conformers were then energetically minimized up to the rms gradient of 0.01. Molegro 2.5 software [1] was used for molecular docking studies and Lead IT 2.3.2 software [2] was used to generate 2D binding poses. LigandScout 4.1 software [3] was used to generate 3D and 2D pharmacophoric maps. The 3D and 2D pharmacophoric maps for the structural features of 2a are displayed in Supplementary Figure S1A,B. The overlay of pharmacophoric map of 2a to pharmacophoric map of the binding of etoposide to TOP IIis shown in Supplementary Figure S1C. Computational studiesComputational studies are useful in the evaluation of physicochemical properties, pharmacokinetics and toxicity of compounds. [4] Lipophilicity and aqueous solubility are the principal properties that affect drug absorption. Thus, the new analogs were studied for the prognosis of Lipinski's rule of five [5] and Veber's criteria [6] using molinspiration software. [7] Also, their carcinogenic properties [8] and drug score values were calculated. [9]