Abstract
Angiogenesis is the process in which the new blood
vessels are formed from pre-existing ones. The development of the vascular
system is one of the earliest events in organogenesis. Since angiogenesis is a
key process in the promotion of cancer and its metastasis (most common cause of
cancer death in human), inhibition of angiogenesis is one of the promising
approaches for treatment of tumor growth and metastasis. In this study, several
derivatives of 4-aryl-4H-chromenes bearing methoxy substituent have been
synthesized with boric acid as catalyst and investigated with potential
anti-angiogenesis effects as well as anti-angiogenic mechanism. Methods:
Anti-angiogenic and anti-proliferative effects of the prepared compounds
checked on three-dimensional culture of human umbilical vein endothelial cells
(HUVECs) in collagen matrix and HUVEC proliferation assay as well as matrix
metalloproteinase (MMP) gelatinase assay in the endothelial cell-based
experimental system. Finally, anti-angiogenic mechanism of the compounds was
identified, using gel zymography method. Results: Among the
synthesized compounds 4a and 4h were as the most active in these series. The
compound 4a was caused angiogenesis inhibition with complete suppression at 3
µg/ml (8.537 µM) and 4h at 1.6 µg/ml (4.196 µM). Conclusion: At
end, chromene derivatives can serve as the lead molecules for further
development of a new class of anti-angiogenesis agents