β-Secretase (BACE1)-inhibiting C-methylrotenoids from Abronia nana suspension cultures.
Suspension cultures of Abronia nana were established to produce C-methylisoflavones. A new C-methylrotenoid, named abronione A (2), was isolated along with three known rotenoids, boeravinone D (1), boeravinone A methyl ether (3), and mirabijalone D (4). The IC50 values of compounds 1, 2, and 4 on β-secretase (BACE1) were 4.77, 62.21, and 4.24 μM, respectively, whereas 3 was inactive. At concentrations up to 1.0 mM, the compounds did not inhibit other proteases such as trypsin, chymotrypsin, and elastase, indicating that they were specific inhibitors of β-secretase. Compounds 1 and 4 were non-competitive inhibitors based on the Dixon plot and with Ki values of 5.01 and 4.28 μM, respectively. At 50 μM, compound 4 inhibited Aβ1-42 production by 43.7% in APPSW-N2a cells.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daehak-ro 80, Sankyuk-dong, Daegu 702-701, Republic of Korea.
Se-Hoon
SH
Park
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daehak-ro 80, Sankyuk-dong, Daegu 702-701, Republic of Korea.
Eun-Ju
EJ
Yang
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daehak-ro 80, Sankyuk-dong, Daegu 702-701, Republic of Korea.
Sang-In
SI
Kim
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daehak-ro 80, Sankyuk-dong, Daegu 702-701, Republic of Korea. Electronic address: kssong@knu.ac.kr.
Kyung-Sik
KS
Song
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D039281:Nyctaginaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007529:Isoflavones; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
Abronia nana; Abronione A; C-Methylrotenoid; β-Secretase inhibitor