In our previous study , 2-(3’-methoxyphenyl)-6-alkylaminoquinolin-4-one (1) was identified as a potent cytotoxicity agents. Compound 1 was evaluated at a maximally tolerance dose with evidence of moderate antitumor activity. In order to search safer antitumor agents , a series of 6-alkylamino- 2-hydroxyphenyl-4-quinolone derivatives were designed and synthesized.
Following published methods , 5-alkylamino-2-aminoacetophenone (4a-4c) were reacted separately with substituted benzoyl chloride (28-35) to yield the correspounding biaryl amide (36-44) which were subsequently cyclized in 1,4 dioxane in the presence of NaOH to give the correspounding substituted 2-phenylquinolin-4-one (45-53). Compounds (45-48、51) were catalytic hydrogenation or demethylated by HBr to afford the correspounding trarget compounds(54-57、60).
The newly synthesized 6-alkylamino-2-hydroxyphenyl-4-quinolone dervatives (54-57、60) were evaluated for cytotoxicity against several human cancer cell lines. The structure-activity relationship was discussed.
Preliminary results showed that 3’-hydroxy-6-morpholinyl-2-phenyl-4- quinolone (55a)、3’-hydroxy-6-pyrrolidinyl-2-phenyl-4-quinolone (55b) and 3’-hydroxy-6-dimethylamino-2-phenyl-4-quinolone (55c)have potent cytotoicity (IC50 values of 0.23-0.009 μM) against HL-60 leukemia cancer cell line with low toxicity against Detroit 551 normal human cell line. These target compounds will be used as new lead compounds for further evaluation.
