Isolation of Bioactive Rotenoids and Isoflavonoids from the Fruits of Millettia caerulea.
Three new rotenoids (1-3), two new isoflavonoids (4 and 5), and six known analogues (6-11) were isolated from an n-hexane partition of a methanol extract of the fruits of Millettia caerulea, with the structures of the new compounds elucidated by analysis of their spectroscopic data. The relative configurations of the rotenoids were determined by interpretation of their NMR spectroscopic data, and their absolute configurations were established using electronic circular dichroism spectra and specific rotation values. All compounds isolated were evaluated for their cell growth inhibitory activity against the HT-29 human colon cancer cell line, and the known compounds, (-)-3-hydroxyrotenone (6) and (-)-rotenone (7), were found to be potently active. When tested in an NF-κB inhibition assay, compound 6 showed activity. This compound, along with the new compound, (-)-caeruleanone D (1), and the known compound, ichthynone (8), exhibited K-Ras inhibitory potency. Further bioactivity studies showed that the new compounds, (-)-3-deoxycaeruleanone D (2) and (-)-3-hydroxycaeruleanone A (3), and the known compounds 8 and 11 induced quinone reductase in murine Hepa 1c1c7 cells.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
Yulin
Y
Ren
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
P Annécie
PA
Benatrehina
Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
Ulyana
U
Muñoz Acuña
Campus Chemical Instrument Center, The Ohio State University, Columbus, Ohio, United States.
Chunhua
C
Yuan
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
Hee-Byung
HB
Chai
Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Tran Ngoc
TN
Ninh
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
Esperanza J
EJ
Carcache de Blanco
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States.
Djaja D
DD
Soejarto
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States.
A Douglas
AD
Kinghorn
D000818:Animals; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D011905:Genes, ras / Q000187:drug effects; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D033641:Millettia / Q000737:chemistry*; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012402:Rotenone / Q000737:chemistry
D007529:Isoflavones; D016328:NF-kappa B; D010936:Plant Extracts; D012402:Rotenone; D016660:NAD(P)H Dehydrogenase (Quinone)