Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins.
Five 4-arylcoumarins (1c-g) and twelve 3,4-dihydro-4-arylcoumarins (2a-l) were synthesized and tested for antioxidant activity, antitumor activity, toxicity and structure-activity relationships analysis. 4-Arylcoumarins and 3,4-dihydro-4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 1d, 1f, 2a, 2f, 2g and 2h had stronger radical scavenging properties than that of vitamin C (Vit C) in ABTS(+) assay. Kinetic traces of scavenging ABTS(+) and DPPH radicals showed that all the reaction could reached endpoint in 1 min, which was similar with Vit C. 4-Arylcoumarins with 3'-hydroxyl-4'-methylphenyl structural show more efficient NO radical scavenging activity. Three compounds 2e, 1f and 2a, in particular had superior EC50 for NO scavenging than did Vit C. MTT assay indicated that one compound in particular had a potential antitumor effect, inhibiting proliferation of BGC-823 cells and almost completely killing them at a concentration 62.5 mg/L. With same concentration 100 μg/mL, hemolytic analysis in rabbit red blood cells showed that only two compounds had hemolytic activity with a little more than 5% hemolysis. Injection and oral toxicity tests on Galleria mellonella larvae showed that none of the tested 4-arylcoumarins significantly affected their appetite, viability and mortality.
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: Keyunzhang@njau.edu.cn.
Keyun
K
Zhang
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China; Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, China; National Key Laboratory of Pharmaceutical New Technology for Chinese Medicine, Kanion Pharmaceutical Corporation, Lianyungang, China.
Weixian
W
Ding
Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, China.
Jie
J
Sun
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
Bin
B
Zhang
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
Fujiao
F
Lu
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China; Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan, China.
Ren
R
Lai
Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, China; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Yong
Y
Zou
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
Gabriel
G
Yedid
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001205:Ascorbic Acid; D045744:Cell Line, Tumor / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects; D011817:Rabbits; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods
D000970:Antineoplastic Agents; D000975:Antioxidants; D003374:Coumarins; D016166:Free Radical Scavengers; C026308:3,4-dihydrocoumarin; D001205:Ascorbic Acid
Antioxidant; Antitumor; Arylcoumarin; Radical scavenging; Structure–activity relationships