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Design,synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead |
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| Authors: | Yung-Yi Cheng Chin-Yu Liu Meng-Tung Tsai Hui-Yi Lin Jai-Sing Yang Tian-Shung Wu Sheng-Chu Kuo Li-Jiau Huang Kuo-Hsiung Lee |
| Affiliation: | 1. Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC;2. Department of Pharmacology, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC;3. Department of Chemistry, National Cheng Kung University, No. 1 Dasyue Road, Tainan, Taiwan, ROC;4. Chinese Medicine Research and Development Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung 40447, Taiwan, ROC;5. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA |
| Abstract: | New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure–activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physicochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound. |
| Keywords: | 2-(Hydroxyphenyl)quinolin-4-one derivatives Antiproliferative activity Anticancer lead development Prodrug |
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