Figures & data
Figure 1. Structure of Sunitinib, SLC-0111, WEG-104, compounds I-II, and target compounds 6a-i, 11a-c and 12a-c.
![Figure 1. Structure of Sunitinib, SLC-0111, WEG-104, compounds I-II, and target compounds 6a-i, 11a-c and 12a-c.](/cms/asset/213179c3-59a4-47f8-a4f8-9c041a83e200/ienz_a_2203389_f0001_c.jpg)
Scheme 1. General procedure for the synthesis of target compounds 6a-i. Reagents and conditions: i) HOSO2Cl, SOCl2 at 0 °C and then rt, 26 h ii) EtOH, ammonia, rt iii) NH2NH2.H2O, AcOH (cat.), and EtOH, reflux, 4 h. iv) EtOH, AcOH (cat.), reflux, 6–8 h.
![Scheme 1. General procedure for the synthesis of target compounds 6a-i. Reagents and conditions: i) HOSO2Cl, SOCl2 at 0 °C and then rt, 26 h ii) EtOH, ammonia, rt iii) NH2NH2.H2O, AcOH (cat.), and EtOH, reflux, 4 h. iv) EtOH, AcOH (cat.), reflux, 6–8 h.](/cms/asset/d69d27c9-dbc7-4488-b531-3e58a38f4074/ienz_a_2203389_sch0001_b.jpg)
Scheme 2. General procedure for the synthesis of target compounds 11a-c and 12a-c. Reagents and conditions: i) K2CO3, acetonitrile, reflux, 5 h; ii) EtOH, AcOH, reflux, 4 h.
![Scheme 2. General procedure for the synthesis of target compounds 11a-c and 12a-c. Reagents and conditions: i) K2CO3, acetonitrile, reflux, 5 h; ii) EtOH, AcOH, reflux, 4 h.](/cms/asset/add3ac95-166b-49cf-a406-423adbaf0a94/ienz_a_2203389_sch0002_b.jpg)
Figure 2. % GI for the highly affected cell lines on treatment by the target isatin derivatives using single dose of 10 μM.
![Figure 2. % GI for the highly affected cell lines on treatment by the target isatin derivatives using single dose of 10 μM.](/cms/asset/1cb1e032-3aaf-4511-8b8d-19ba9c48ba11/ienz_a_2203389_f0002_c.jpg)
Table 1. Cytotoxicity of selected compounds 6f, 6i, 11b-c, and 12a-c (IC50) against T47D cells.
Table 2. IC50 values of selected compounds 6f, 11b-c, and 12b against VEGFR-2 and CA inhibition activity.
Figure 4. Apoptosis rate quantification (%) and necrosis in (A) flow cytometry, effect of (B) control, (C) 11b and (D) 12b on annexin V-FITC-positive staining (%) in T47D cell line.
![Figure 4. Apoptosis rate quantification (%) and necrosis in (A) flow cytometry, effect of (B) control, (C) 11b and (D) 12b on annexin V-FITC-positive staining (%) in T47D cell line.](/cms/asset/fd11214c-8d23-4b28-9a32-06eb76e1f53c/ienz_a_2203389_f0004_c.jpg)
Figure 5. Docking of 12b inside the active site of VEGFR-2 receptor (code: 4ASD); active site view (top) and 2D schematic view of the interactions (bottom).
![Figure 5. Docking of 12b inside the active site of VEGFR-2 receptor (code: 4ASD); active site view (top) and 2D schematic view of the interactions (bottom).](/cms/asset/eea1eb45-1dfb-41b8-8ea6-2fd0cae9bd27/ienz_a_2203389_f0005_c.jpg)
Figure 6. From left to right: (A) Temperature, (B) pressure and (C) potential energy during the 100 ns MD simulations.
![Figure 6. From left to right: (A) Temperature, (B) pressure and (C) potential energy during the 100 ns MD simulations.](/cms/asset/c0d44529-759a-449b-be5e-4de8bf0fe0ce/ienz_a_2203389_f0006_c.jpg)
Figure 7. RMSD, Radius of gyration and average centre of mass distance of heavy atoms of 12b during 100 ns MD simulation.
![Figure 7. RMSD, Radius of gyration and average centre of mass distance of heavy atoms of 12b during 100 ns MD simulation.](/cms/asset/d2c7aede-9886-4f61-9830-b3100e85fcc3/ienz_a_2203389_f0007_c.jpg)
Figure 9. Different types of interaction exhibited by 12b with the amino acids within the active site of VEGFR-2 during the whole MD simulation frames.
![Figure 9. Different types of interaction exhibited by 12b with the amino acids within the active site of VEGFR-2 during the whole MD simulation frames.](/cms/asset/70419654-c68a-4756-8231-d7de11b6d5aa/ienz_a_2203389_f0009_c.jpg)
Table 3. Free binding energies of 12b with VEGFR-2 in kJ/mol.