Antitumor agents 278. 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs as potent in vitro anti-cancer agents.
4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs were designed, synthesized, and evaluated for cytotoxic activity. Among all 4-substituted ABO analogs, cyclohexyl (12), N-methoxy-N-methylacetamide (14), and various aromatic derivatives (15-25 and 27) exhibited promising cell growth inhibitory activity with ED(50) values of 0.01-5.8 microM against all tested tumor cell lines. The 4'-methoxyphenyl derivative (18) and 3'-methylphenyl derivative (24) showed the most potent antitumor activity against a broad range of cancer cell lines with ED(50) values of 0.01-76 microM. Preliminary SAR results indicated that substitutions on nitrogen are critical to the antitumor potency.
Dong
Yizhou
Y
Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, United States.
Nakagawa-Goto
Kyoko
K
Lai
Chin-Yu
CY
Morris-Natschke
Susan L
SL
Bastow
Kenneth F
KF
Lee
Kuo-Hsiung
KH
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002867:Chromones