https://orcid.org/0000-0002-4648-5184
Figures & data
Figure 1. Potent anti-proliferative agents containing pyrimidines, cyclohexenones, and selenadiazoles.
Figure 2. Design of scaffolds I and II as dual inhibitors of Topoisomerase II and HSP90.
Scheme 1. Synthesis of compounds 3a–f.
Scheme 2. Synthesis of compounds 4 and 5a–e.
Scheme 3. Synthesis of compound 7.
Table 1. Anti-proliferative activity of compounds 3a–f, 5a–e, and 7 against HepG2, A-549, and MCF-7 cell lines.
Table 2. The in vitro cytotoxic activity of compounds 3a and 5d against WI-38 cell lines compared to doxorubicin.
Table 3. The in vitro inhibitory activity of Topoisomerase II and HSP90 enzymes for compounds 3a and 5d, compared to doxorubicin and geldanamycin, respectively.
Figure 3. Effect of compound 3a on HepG-2 cell cycle distribution using propidium iodide flow-cytometry assay.
Figure 4. Apoptosis induced by 3a on HepG-2 cells using Annexin FITC/PI dual staining assay.
Figure 5. The effect of 3a on the expression of genes encoding caspase-3, Topoisomerase II, and HSP90 in the supernatant of HepG-2 cell lines.
Figure 6. 2D & 3D representation of dexrazoxane (a), 2D representation of 3a & 3D representation of overlay view of 3a and dexrazoxane (b), 2D representation of 5d & 3D representation of overlay view of 5d and dexrazoxane (c) at the binding site of Topoisomerase II (1QZR).
Figure 7. 2D & 3D representation of geldanamycin (a), 2D representation of 3a & 3D representation of overlay view of 3a and geldanamycin (b), 2D representation of 5d & 3D representation of overlay view of 5d and geldanamycin (c) at the binding site of HSP90 (1YET).
Table 4. Docking results for the prepared compounds at Topoisomerase II (1QZR) and HSP90 (1YET) binding sites.
Figure 8. The geometry-optimised structure of 3a compound.
Table 5. Optimised geometrical parameters for the structure of 3a computed at B3LYP/6-31G*.
Table 6. Mulliken atomic charges of 3a calculated at DFT/B3LYP/6-31G* level of theory.
Figure 9. The atomic orbital compositions of the molecular orbital for 3a.
Table 7. molecular orbital energies, HOMO-LUMO gap, and global reactivity descriptors for 3a, calculated at B3LYP/6-31G* level.
Figure 10. The total electron density surface was mapped with a molecular electrostatic potential MEP plot for Sparfloxacin calculated using the B3LYP/6-31G* method.
Table 8. Physicochemical properties and drug likeness for compounds 3a and 5d.
Table 9. The ADME study results for compounds 3a and 5d.
Table 10. In silico toxicity properties for compounds 3a and 5d.