Assessing the Antiangiogenic Effects of Chalcones and Their Derivatives
Burmaoglu, Serdar, Gobek, Arzu, Anil, Derya Aktas, Alagoz, Mehmet Abdullah, Guner, Adem, Guler, Cem, Hepokur, Ceylan, Yavasoglu, N. Ulku Karabay, Algul, Oztekin
Pathological angiogenesis plays a critical role in tumorigenesis and tumor progression, 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 provided a basis for further design, structural modification, and development of chalcone derivatives as new anti-angiogenic agents.
- Journal
- POLYCYCLIC AROMATIC COMPOUNDS
- Year
- 2024
- Volume
- 44
- Issue
- 1
- Pages
- 51-66
- ISSN
- 1040-6638
- eISSN
- 1563-5333
- DOI
- 10.1080/10406638.2023.2167216
- WoS UID
- WOS:000915991900001