Bioactive 5,6-dihydro-alpha-pyrone derivatives from Hyptis brevipes.
Six new 5,6-dihydro-alpha-pyrone derivatives (1-6), namely, brevipolides A-F, together with seven known compounds, including a 5,6-dihydro-alpha-pyrone derivative (7), three flavonoids, a steroid glycoside, and two triterpenoids, were isolated from the entire plant of Hyptis brevipes. Compounds 1-7 were assigned with the absolute configuration 5R, 6S, 7S, and 9S, as elucidated by analysis of data obtained from their CD spectra and by Mosher ester reactions. Compounds 2, 6, and 7 exhibited ED(50) values of 6.1, 6.7, and 3.6 microM against MCF-7 cells, and compounds 1, 2, 6, and 8 (the known 5,6,3'-trihydroxy-3,7,4'-trimethoxyflavone) gave ED(50) values of 5.8, 6.1, 7.5, and 3.6 microM against HT-29 cells, respectively. However, no significant cytotoxicity was found against Lu1 cells for any of the compounds isolated. When these compounds were subjected to evaluation in a panel of mechanism-based in vitro assays, compound 7 was found to be active in an enzyme-based ELISA NF-kappaB assay, with an ED(50) value of 15.3 microM. In a mitochondrial transmembrane potential assay, compounds 3, 7, and 8 showed ED(50) values of 8.5, 75, and 310 nM, respectively. No potent activity was found in a proteasome inhibition assay for any of the isolated compounds.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Ye
Y
Deng
Marcy J
MJ
Balunas
Jeong-Ah
JA
Kim
Daniel D
DD
Lantvit
Young-Won
YW
Chin
Heebyung
H
Chai
Sugeng
S
Sugiarso
Leonardus B S
LB
Kardono
Harry H S
HH
Fong
John M
JM
Pezzuto
Steven M
SM
Swanson
Esperanza J Carcache
EJ
de Blanco
A Douglas
AD
Kinghorn
D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D031331:Hyptis / Q000737:chemistry*; D007214:Indonesia; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005419:Flavonoids; D016328:NF-kappa B; D011753:Pyrones