Supplementary material. Development and Investigations of Thiazolidinedione & Pyrazoline Compounds as Antiangiogenic Weapons Targeting VEGFR-2.

Table S1. HUVECs IC50 of test compounds.

Table S2. VEGFR-2 IC50 of test compounds.

Table S3. Migration assay

Table S4. Tube formation assay.

Table S5. CAM assay of compounds.

Table S6: Docking Scores for indicated compound docked into 4 different crystal structures of VEGFR-2. Columns with scores are headed by PDB-ID’s.

Figure S1. Migration Assay of HUVECs after 8 h of (A) untreated, (B) staurosporine (10 µM), (C) B1 (10 µM), (D) B2 (10 µM), and (E) PB16 (10 µM) treatments.

Figure S2. Tube Formation Assay of HUVECs after 48 h of (A) untreated, (B) staurosporine (10 µM), (C) B1 (10 µM), (D) B2 (10 µM), and (E) PB16 (10 µM) treatments.

Figure S3. CAM Assay of (A) untreated, (B) staurosporine (10 µg/µL), (C) B1 (10 µg/µL), and (D) PB16 (10 µg/µL) treatments.

Figure S4: Redocking of ligands into crystal structures of VEGFR-2 with the following PDB-ID’s: A) 3VHE, B) 3WZE, C) 6XVK and D) 4ASD. The RMSD-values between redocked and crystallized ligand are indicated and demonstrate excellent overlap and suitability of the applied docking protocol.

Figure S5: Overlay of docking poses of A) (S)-B1, B) (R)-B1 and C) PB16 into four different crystal structures of VEGFR-2 receptor. Docking poses are colored according to the corresponding receptor structure with the

following PDB-ID’s: 3VHE (green), 3WZE (magenta), 6XVK (orange), 4ASD (dark brown)

Figure S6: Overall structures of VEGFR-2 in complex with A) sorafenib (PDB-ID: 3WZE), B) PB16, C) (S)-B1, and D) (R)-B1. The surface of the binding channel is clipped and colored cyan.

Structural characterization