4-substituted-4-hydroxycyclohexa-2, 5-dien-1-ones with selective activities against colon and renal cancer cell lines

Wells, G., Berry, J.M., Bradshaw, T.D., Burger, A.M., Seaton, A., Wang, B., Westwell, A.D. and Stevens, M.F.G. (2003) 4-substituted-4-hydroxycyclohexa-2, 5-dien-1-ones with selective activities against colon and renal cancer cell lines. Journal of Medicinal Chemistry, 46 . pp. 532-541. 10.1021/jm020984y .

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DOI: 10.1021/jm020984y

Abstract

The synthesis and antitumor evaluation of a series of new heteroaromatic- and aromatic-substituted hydroxycyclohexadienones ("quinols"), and their imine counterparts, are described. The quinols were synthesized via the addition of a lithiated aromatic moiety to a quinone ketal followed by deprotection. When the aromatic portion of the molecule is a fused heterobicyclic structure (e.g., benzothiazole derivative 7a), potent in vitro antitumor activity was observed in HCT 116 (GI50 = 40 nM) and HT 29 (GI50 = 380 nM) human colon as well in as MCF-7 and MDA 468 human breast cancer cell lines. When examined on the NCI Developmental Therapeutics Screening Program in vitro screen (60 human cancer cell lines), active compounds in this series consistently displayed a highly unusual pattern of selectivity; cytotoxicity (LC50) was concentrated in certain colon and renal cell lines only. Analogue 7a also showed in vivo antitumor activity against human RXF 944XL renal xenografts in nude NMRI mice and is the focus of further study.

Item Type:Article
Additional Information:Full text available electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:981
Journal or Publication Title:Journal of Medicinal Chemistry
Deposited By:Library Staff
Deposited On:02 Jun 2008 15:44
Last Modified:12 May 2011 17:53

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