Discovery of pyridine- sulfonamide hybrids as a new scaffold for the development of potential VEGFR-2 inhibitors and apoptosis inducers

Marwa F Ahmed; Eman Y Santali

doi:10.1016/j.bioorg.2021.104842

Discovery of pyridine- sulfonamide hybrids as a new scaffold for the development of potential VEGFR-2 inhibitors and apoptosis inducers

Bioorg Chem. 2021 Jun:111:104842. doi: 10.1016/j.bioorg.2021.104842. Epub 2021 Mar 22.

Authors

Marwa F Ahmed¹, Eman Y Santali²

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt. Electronic address: marwa.farg@tu.edu.sa.
² Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

PMID: 33798847
DOI: 10.1016/j.bioorg.2021.104842

Abstract

New sulfonamide derivatives have been synthesized and tested as antitumor agents. All newly synthesized compounds were tested in vitro against 60 lines of human cancer cells. Compound VIIb shows broad-spectrum activity with a mean inhibition value of 91.67% against all cell lines. It exhibited potent anticancer activity with GI50 values of 1.06-8.92 μM relative to most of the tested cancer cell lines. Compound VIIb has been tested for enzyme inhibition activity toward vascular endothelial growth factor receptor 2, where VEGFR-2 was potently inhibited at a lower IC50 value of 3.6 μM, compared with sorafenib (IC50 = 4.8 μM). Hybrid VIIb was also able to induce cell cycle disturbance and apoptosis in Renal UO-31 cells, as shown by DNA flow cytometry and Annexin V-FITC/PI assays. It has also revealed lower Bcl-2 protein expression anti-apoptotic levels and higher BAX, p53, and caspases 3 expression levels.

Keywords: Antitumor; Apoptosis; Cell cycle; Sulfonamides; Vascular endothelial growth factor receptor.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Cycle / drug effects
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Discovery*
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemistry
Pyridines / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Pyridines
Sulfonamides
KDR protein, human
Vascular Endothelial Growth Factor Receptor-2
pyridine