Cytotoxic 2',5'-dihydroxychalcones with unexpected antiangiogenic activity.
A series of 2',5'-dihydroxychalcones were synthesized and evaluated for cytotoxicity against tumor cell lines and human umbilical venous endothelial cells (HUVEC). It was found that chalcones with electron-withdrawing substituents on the B ring exhibited potent cytotoxicity against a variety of tumor cell lines while compounds with electron-releasing groups were less potent in general. Those compounds with B ring replaced by extended or heteroaromatic rings exhibited significant bioactivity. Several compounds were shown to have marked cytotoxic selectivity towards HUVECs. Especially, among the synthesized compounds, 2-chloro-2',5'-dihydroxychalcone (2-3) showed the highest selectivity index up to 66 in comparison to HCT116 cells. This compound also exhibited strong inhibitory effects on the HUVEC tube formation in an in vitro model. When administered into BDF1 mice bearing Lewis lung carcinoma cells at 50 mg kg(-1) day(-1), 2-3 was found to inhibit the growth of tumor mass by 60.5%.
Nam
Nguyen-Hai
NH
College of Pharmacy, Chungnam National University, Taejon, 305-764, South Korea.
Kim
Yong
Y
You
Young-Jae
YJ
Hong
Dong-Ho
DH
Kim
Hwan-Mook
HM
Ahn
Byung-Zun
BZ
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002599:Chalcone