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

Upadhyay N 1 , Tilekar K 1 , Safuan S 2 , Kumar AP 3 , Schweipert M 4 , Meyer-Almes FJ 4 Show all authors , Ramaa CS 1

Affiliations 

  • 1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, Navi Mumbai, 400614, India
  • 2 Universiti Sains Malaysia School of Health Sciences, Health Campus Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
  • 3 Cancer Science Institute of Singapore & Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 4 Department of Chemical Engineering & Biotechnology, University of Applied Sciences, Darmstadt, Germany
Future Med Chem, 2021 11;13(22):1963-1986.
PMID: 34581188 DOI: 10.4155/fmc-2021-0139

Abstract

Background: Angiogenesis deregulation is often linked to cancer and is thus an essential target. Materials & methods: Twenty-nine compounds were developed as VEGFR-2 inhibitors. Compounds were evaluated to determine their antiangiogenic activity. Results: B1, PB11 and PB16 showed HUVEC's IC50 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. Conclusion: These compounds can target VEGFR-2 and are endowed with in vitro and in vivo antiangiogenic activity.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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