Natural inhibitors of carcinogenesis.
Previous collaborative work by our group has led to the discovery of several plant isolates and derivatives with activities in in vivo models of cancer chemoprevention, including deguelin, resveratrol, bruceantin, brassinin, 4'-bromoflavone, and oxomate. Using a panel of in vitro bioassays to monitor chromatographic fractionation, a diverse group of plant secondary metabolites has been identified as potential cancer chemopreventive agents from mainly edible plants. Nearly 50 new compounds have been isolated as bioactive principles in one or more in vitro bioassays in work performed over the last five years. Included among these new active compounds are alkaloids, flavonoids, stilbenoids, and withanolides, as well as a novel stilbenolignan and the first representatives of the norwithanolides, which have a 27-carbon atom skeleton. In addition, over 100 active compounds of previously known structure have been obtained. Based on this large pool of potential cancer chemopreventive compounds, structure-activity relationships are discussed in terms of the quinone reductase induction ability of flavonoids and withanolides and the cyclooxygenase-1 and -2 inhibitory activities of flavanones, flavones and stilbenoids. Several of the bioactive compounds were found to be active when evaluated in a mouse mammary organ culture assay, when used as a secondary discriminator in our work. The compounds (2 S)-abyssinone II, (2 S)-2',4'-dihydroxy-2"-(1-hydroxy-1-methylethyl)dihydrofuro[2,3- h]-flavanone, 3'-[gamma-hydroxymethyl-( E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'- O-coumarate, isolicoflavonol, isoliquiritigenin, and ixocarpalactone A are regarded as promising leads as potential cancer chemopreventive agents.
Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. kinghorn.4@osu.edu
A Douglas
AD
Kinghorn
Bao-Ning
BN
Su
Dae Sik
DS
Jang
Leng Chee
LC
Chang
Dongho
D
Lee
Jian-Qiao
JQ
Gu
Esperanza J
EJ
Carcache-Blanco
Alison D
AD
Pawlus
Sang Kook
SK
Lee
Eun Jung
EJ
Park
Muriel
M
Cuendet
Joell J
JJ
Gills
Krishna
K
Bhat
Hye-Sung
HS
Park
Eugenia
E
Mata-Greenwood
Lynda L
LL
Song
Meishiang
M
Jang
John M
JM
Pezzuto
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D010936:Plant Extracts