Figures & data
Figure 1. Some previously reported topoisomerase II inhibitors and DNA intercalators display their pharmacophoric characteristics.
![Figure 1. Some previously reported topoisomerase II inhibitors and DNA intercalators display their pharmacophoric characteristics.](/cms/asset/0957eb3f-deb0-4b3a-b35a-3913377e30ae/ienz_a_2171029_f0001_c.jpg)
Figure 2. The 2D (A) and 3D (B) illustrations display the superimposition of the native co-crystallised EVP and redocked one (Mauve and Light Blue, respectively, in 3D picture) at the topoisomerase II-DNA complex (PDB entry: 3QX3) with RMSD value 1.42 Å.
![Figure 2. The 2D (A) and 3D (B) illustrations display the superimposition of the native co-crystallised EVP and redocked one (Mauve and Light Blue, respectively, in 3D picture) at the topoisomerase II-DNA complex (PDB entry: 3QX3) with RMSD value 1.42 Å.](/cms/asset/0305ccd3-459a-46b0-b552-4eebdf6ce885/ienz_a_2171029_f0002_c.jpg)
Table 1. The binding free energy scores, RMSD values, and binding interactions of the most promising compounds (SP, RO, AZ, CL, and ER) along with the co-crystallised ligand (EVP) into DNA–topoisomerase II complex.
Figure 3. 2D (A) and 3D (B) illustrations revealing the binding interactions of the re-docked co-crystallised ligand (EVP) at the topoisomerase II-DNA complex active site, where red dashed lines stand for H-bonds, and black ones stand for H-pi bonds.
![Figure 3. 2D (A) and 3D (B) illustrations revealing the binding interactions of the re-docked co-crystallised ligand (EVP) at the topoisomerase II-DNA complex active site, where red dashed lines stand for H-bonds, and black ones stand for H-pi bonds.](/cms/asset/7d09d81a-1f2c-435d-8005-aacc54235a24/ienz_a_2171029_f0003_c.jpg)
Figure 4. The 2D and 3D binding interactions of compounds AZ (A,B), CL (C,D), and ER (E,F) reveal their binding interactions at the topoisomerase II-DNA complex active site.
![Figure 4. The 2D and 3D binding interactions of compounds AZ (A,B), CL (C,D), and ER (E,F) reveal their binding interactions at the topoisomerase II-DNA complex active site.](/cms/asset/021bf679-7109-43b8-8a8c-624fa2eae611/ienz_a_2171029_f0004_c.jpg)
Figure 5. The 2D and 3D binding interactions of compounds RO (A,B), and SP (C,D) reveal their binding interactions at the topoisomerase II-DNA complex active site (PDB: 3QX3).
![Figure 5. The 2D and 3D binding interactions of compounds RO (A,B), and SP (C,D) reveal their binding interactions at the topoisomerase II-DNA complex active site (PDB: 3QX3).](/cms/asset/e8717619-44cb-46d6-9d93-714163bc1f8b/ienz_a_2171029_f0005_c.jpg)
Figure 6. The RMSD of the six complexes (SP, RO, AZ, CL, and ER) within the topoisomerase II-DNA complex compared to the co-crystallised (EVP) inhibitor as a function of simulation time (200 ns).
![Figure 6. The RMSD of the six complexes (SP, RO, AZ, CL, and ER) within the topoisomerase II-DNA complex compared to the co-crystallised (EVP) inhibitor as a function of simulation time (200 ns).](/cms/asset/0388267b-b640-42d0-b3ee-dfa8f67843ee/ienz_a_2171029_f0006_c.jpg)
Figure 7. The RMSD of the ligands (SP, RO, AZ, CL, and ER) within the topoisomerase II-DNA complex compared to the co-crystallised (EVP) inhibitor as a function of simulation time (200 ns).
![Figure 7. The RMSD of the ligands (SP, RO, AZ, CL, and ER) within the topoisomerase II-DNA complex compared to the co-crystallised (EVP) inhibitor as a function of simulation time (200 ns).](/cms/asset/685822ad-4ea5-498f-9911-c7770fd8c07d/ienz_a_2171029_f0007_c.jpg)
Figure 8. Histograms indicating the fractions of binding between the protein’s amino acids and its ligand for (A) SP-3QX3, (B) RO-3QX3, (C) AZ-3QX3, (D) CL-3QX3, (E) ER-3QX3, and (F) EVP-3QX3 complexes.
![Figure 8. Histograms indicating the fractions of binding between the protein’s amino acids and its ligand for (A) SP-3QX3, (B) RO-3QX3, (C) AZ-3QX3, (D) CL-3QX3, (E) ER-3QX3, and (F) EVP-3QX3 complexes.](/cms/asset/9eb0fabd-9745-4dea-995e-e5f0224f0fe3/ienz_a_2171029_f0008_c.jpg)
Table 2. Prime MM-GBSA energies for compounds SP, RO, AZ, CL, ER, and EVP at the binding pocket of the topoisomerase II-DNA complex.
Figure 10. Inhibitory potential (IC50) of the most promising and commercially available antibiotics (SP, RO, AZ, CL, and ER) against MCF-7, HepG2, and HCT-116.
![Figure 10. Inhibitory potential (IC50) of the most promising and commercially available antibiotics (SP, RO, AZ, CL, and ER) against MCF-7, HepG2, and HCT-116.](/cms/asset/d7563287-0231-455c-aef9-998ff344042d/ienz_a_2171029_f0010_c.jpg)
Figure 11. (A) The measured IC50 of tested antibiotics (SP, RO, AZ, CL, and ER) on TOP-2 compared to DOX. (B) Gel electrophoresis image representing the variable decatenation potential of DNA by TOP-2 as inhibited by DOX and the tested antibiotics (SP, RO, AZ, CL, and ER). The N Lane represents no TOP-2 activity while the P lane is the uninhibited enzyme.
![Figure 11. (A) The measured IC50 of tested antibiotics (SP, RO, AZ, CL, and ER) on TOP-2 compared to DOX. (B) Gel electrophoresis image representing the variable decatenation potential of DNA by TOP-2 as inhibited by DOX and the tested antibiotics (SP, RO, AZ, CL, and ER). The N Lane represents no TOP-2 activity while the P lane is the uninhibited enzyme.](/cms/asset/5585d88a-17ed-40d9-aafa-a19d41166761/ienz_a_2171029_f0011_c.jpg)