| dc.description.abstract | Pathological angiogenesis plays a critical role in tumorigenesis and tumor pro gression, and anti-angiogenesis therapies have evinced promising antitumor
effects in solid tumors. Chalcone skeleton has been regarded as a potential
antitumor agent that also targets angiogenesis. In this study, we designed
twenty-one non-fluoro-substituted chalcones (13–18, 24–27) and saturated
chalcone derivatives (19–23, 28–33) as anti-angiogenic compounds. During
the initial stage, these compounds were assessed for their anti-cancer activities
against MCF-7 cancer cell lines according to the MTT assay. The compounds
revealed satisfactory anti-proliferative capability. An ex vivo fertilized hens’
egg-chorioallantoic membrane (HET-CAM) angiogenic study was conducted
for the compounds to gauge their mortality and toxicity, which, in turn,
revealed a potent anti-angiogenic effect. Eight compounds (16, 17, 21, 24, 26,
27, 29, and 31) significantly reduced densities of capillaries on CAM, whereas
compounds 27 and 29 were the most effective anti-angiogenic agents, when
compared with Suramin. Moreover, RT-qPCR analysis demonstrated that the
anti-angiogenic activity was associated with the fold changes of VEGFR2.
Molecular docking studies were conducted for compounds to investigate their
mode of interaction within the binding site of VEGFR-2 kinases. This work pro vided a basis for further design, structural modification, and development of
chalcone derivatives as new anti-angiogenic agents. | tr |
