Compounds obtained from sida acuta with the potential to induce quinone reductase and to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture model.
Activity-guided fractionation of the EtOAc-soluble extract of the whole plants of Sida acuta using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells, led to the isolation of ten active compounds of previously known structure, quindolinone (1), cryptolepinone (2), 11-methoxyquindoline (3), N-trans-feruloyltyramine (4), vomifoliol (5), loliolide (6), 4-ketopinoresinol (7), scopoletin (8), evofolin-A (9), and evofolin-B (10), along with five inactive compounds of known structure, ferulic acid, sinapic acid, syringic acid, (+/-)-syringaresinol, and vanillic acid. These isolates were identified by physical and spectral data measurement. A new derivative of quindolinone, 5,10-dimethylquindolin-11-one (1a) was synthesized and characterized spectroscopically. Of the active substances, compounds 1-3 and 1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 microg/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2), N-trans-feruloyltyramine (4), and 5,10-dimethylquindolin-11-one (1a) found to exhibit 83.3, 75.0, and 66.7% inhibition of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions, respectively, at a dose of 10 microg/mL.
Jang
Dae Sik
DS
Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
Park
Eun Jung
EJ
Kang
Young-Hwa
YH
Su
Bao-Ning
BN
Hawthorne
Michael E
ME
Vigo
Jose Schunke
JS
Graham
James G
JG
Cabieses
Fernando
F
Fong
Harry H S
HH
Mehta
Rajendra G
RG
Pezzuto
John M
JM
Kinghorn
A Douglas
AD
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D023401:Animal Use Alternatives; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D019660:Malvaceae / Q000737:chemistry*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene; D016660:NAD(P)H Dehydrogenase (Quinone)