Neuroprotective coumarins from the root of Angelica gigas: structure-activity relationships.
An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae) exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Using neuroprotective activity-guided fractionation, nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-beta-D-glucopyranoside (3), (S)-peucedanol-7-O-beta-D-glucopyranoside (4), (S)-peucedanol-3'-O-beta-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7), isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3, exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from 0.1 to 10 microM. To explore the structure-activity relationships of coumarins, sixteen previously isolated compounds; 10-25, were simultaneously evaluated in the same system. Our results revealed that cyclization of the isoprenyl group, such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of coumarin, as well as lipophilicity played an important role in the neuroprotective activity of coumarins.
Kang
So Young
SY
Division of Food Science and Aqualife Medicine, Chonnam National University, Yeosu, Chonnam 550-749, Korea. sykang1@chonnam.ac.kr
Kim
Young Choong
YC
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D003374:Coumarins; D018696:Neuroprotective Agents; D018698:Glutamic Acid