Abstract

Numerous studies in vivo, as well as in vitro, have shown that compounds of the vitamin A group, their derivatives, or their analogs (collectively called retinoids) may prevent or reverse carcinogen-induced malignacy. Although much progress has already been made in developing retinoids for the chemoprevention of cancer, new retinoids with improved chemopreventive activity, lower toxicity, and superior pharmacokinetic properties must be found in order to make chemoprevention a more effective method of cancer control. For these reasons, new retinoids of diverse structures must be synthesized for evaluations of chemopreventive activity, pharmacological investigations, and biochemical studies. In order to explore further the effects of structural modification on chemopreventive activity, this program of synthesis of new retinoids is comprised (1) of derivatives of retinoids with known activity and (2) of new types of retinoid structures. Some of the new retinoids will be derivatives of retinol and retinoic acid. Some of the new types of retinoids will be modified in structure at, or near, the polar, terminal group. Other groups of new retinoids will be modified in the cyclohexenyl group, and in some the cyclohexenyl group will be replaced.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA034968-02
Application #
3093601
Study Section
Cancer Therapeutics Program Project Review Committee (CTR)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205

  Publications

Shealy, Y Fulmer; Riordan, James M; Frye, Jerry L et al. (2003) Inhibition of papilloma formation by analogues of 7,8-dihydroretinoic acid. J Med Chem 46:1931-9
Shealy, Y F; Hill, D L; Sani, B P et al. (1998) Anhydroretinol, a retinoid active in preventing mammary cancer induced in rats by N-methyl-N-nitrosourea. Oncol Rep 5:857-60
Muccio, D D; Brouillette, W J; Breitman, T R et al. (1998) Conformationally defined retinoic acid analogues. 4. Potential new agents for acute promyelocytic and juvenile myelomonocytic leukemias. J Med Chem 41:1679-87
Shealy, Y F; Frye, J L; Hill, D L et al. (1998) Retinyl substituted-benzyl ethers. Inhibition of mammary carcinogenesis by retinyl 3,4,5-trimethoxybenzyl ether (RTMBE). Anticancer Drug Des 13:159-82
Shih, T W; Lin, T H; Shealy, Y F et al. (1997) Nonenzymatic isomerization of 9-cis-retinoic acid catalyzed by sulfhydryl compounds. Drug Metab Dispos 25:27-32
Sani, B P; Venepally, P R; Levin, A A (1997) Didehydroretinoic acid: retinoid receptor-mediated transcriptional activation and binding properties. Biochem Pharmacol 53:1049-53
Shimada, T; Ross, A C; Muccio, D D et al. (1997) Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid receptor-selective retinoids. Arch Biochem Biophys 344:220-7
Shealy, Y F; Frye, J L; Riordan, J M et al. (1997) Retinyl ethers as cancer chemopreventive agents. Suppression of mammary cancer. Anticancer Drug Des 12:15-33
Sani, B P; Zhang, X; Hill, D L et al. (1996) Retinyl methyl ether: binding to transport proteins and effect on transcriptional regulation. Biochem Biophys Res Commun 223:293-8
Lin, T H; Rogers, T S; Hill, D L et al. (1996) Murine toxicology and pharmacology of UAB-8, a conformationally constrained analog of retinoic acid. Toxicol Appl Pharmacol 139:310-6

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