Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

WANG Fenghua; WANG Kai; SHEN Jianhua; CHEN Kaixian

doi:10.11665/j.issn.1000-5048.20140306

Journal of China Pharmaceutical University > 2014 > 45(3): 286-292. > DOI: 10.11665/j.issn.1000-5048.20140306

WANG Fenghua, WANG Kai, SHEN Jianhua, CHEN Kaixian. Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds[J]. Journal of China Pharmaceutical University, 2014, 45(3): 286-292. DOI: 10.11665/j.issn.1000-5048.20140306

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Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

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A combination of the structural features of dihydromyricetin and quinolone antineoplastic compounds gave rise to 3-hydroxy-4-quinolone motif. Starting from 3, 5-dimethoxyaniline, the target compounds were prepared through a reaction cascade, including reductive amination, Friedel-Crafts reaction, microwave assisted ring closure, BBr₃ catalyzed demethylation and Mannich reaction. Sixteen novel compounds were synthesized, and their structures were confirmed by IR, MS and ¹H NMR. The antiproliferative activities of the compounds against A549 and NCI-H 460 cells were tested in MTT assay. Several compounds exhibited moderate antiproliferative activities against both cell lines, of which, compound 11b displayed the most robust inhibition towards NCI-H 460. Preliminary structural-activity relationships indicated that introduction of isopentenyl into the N-1 position of 3-hydroxy-4-quinolone motif would significantly improve the potency of the compounds.
- 3-hydroxy-4-quinolone,
- combination,
- synthesis,
- antiproliferative activity,
- structural-activity relationship

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Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

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