Development and investigation of thiazolidinedione and pyrazoline compounds as antiangiogenic weapons targeting VEGFR-2

• Published in: Future medicinal chemistry 2021-11, Vol.13 (22), p.1963-1986
• Main Authors: Upadhyay, Neha, Tilekar, Kalpana, Safuan, Sabreena, Kumar, Alan P, Schweipert, Markus, Meyer-Almes, Franz-Josef, Ramaa, C S
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; antiangiogenic; diaryl-pyrazoline; Drug Development; Humans; Neovascularization, Physiologic - drug effects; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; thiazolidinedione; Thiazolidinediones - chemical synthesis; Thiazolidinediones - chemistry; Thiazolidinediones - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGFR-2
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2021-0139

Angiogenesis deregulation is often linked to cancer and is thus an essential target. Twenty-nine compounds were developed as VEGFR-2 inhibitors. Compounds were evaluated to determine their antiangiogenic activity. B1, PB11 and PB16 showed HUVEC's IC  scores in the submicromolar range. B1, B2 and PB16 reduced cellular migration and capillary tube formation of HUVECs. VEGFR-2 inhibitory activity was found in the nanomolar range: 200 nM of B1, 500 nM of B2 and 600 nM of PB16. B1 and PB16 suppressed the formation of new capillaries on growing CAMs. B1 and PB16 occupied the ATP site and allosteric pocket of VEGFR-2 in docking studies. These compounds can target VEGFR-2 and are endowed with and antiangiogenic activity.