Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase.
Vascular endothelial growth factor Receptor-2 (VEGFR-2) kinase inhibition is one of the well established strategies to promptly tackle tumor growth by suppression of angiogenesis. In the current study, structure-based virtual screening methodology of a series of quinolyl-thienyl chalcones indicated their strong potential as VEGFR-2 kinase inhibitors. In vitro VEGFR-2 kinase inhibitory activity was found to be significant (compound 19, IC(50): 73.41nM). All compounds showed significant inhibition of human umbilical vein endothelial cells (HUVEC) proliferation (compound 19, IC(50): 21.78nM). Molecular interactions of the compounds were studied using molecular docking studies.
Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
Syed Umar Farooq
SU
Rizvi
Hamid Latif
HL
Siddiqui
Muhammad
M
Nisar
Nematullah
N
Khan
Inamullah
I
Khan
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D047188:Chalcones; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D013876:Thiophenes; D040301:Vascular Endothelial Growth Factor Receptor-2