Sterols as Anticancer Agents: Synthesis of Ring-B Oxygenated Steroids, Cytotoxic Profile, and Comprehensive SAR Analysis

The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ5-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer c...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2010-11, Vol.53 (21), p.7632-7638
Main Authors: Carvalho, João F. S, Silva, M. Manuel Cruz, Moreira, João N, Simões, Sérgio, Sá e Melo, M. Luisa
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Cell Line
Cell Line, Tumor
Cell Proliferation - drug effects
Cisplatin - administration & dosage
Doxorubicin - administration & dosage
Drug Screening Assays, Antitumor
Drug Synergism
Humans
Sterols - chemical synthesis
Sterols - chemistry
Sterols - pharmacology
Structure-Activity Relationship
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Summary:The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ5-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cells (leukemia) being particularly sensitive to 4, 8, 22, and 27 (IC50 < 5.6 μM). The structural requirements to induce selective toxicity are discussed to shed light on the development of new anticancer drugs.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm1007769