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 Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cells (leukemia) being particularly sensitive to 4, 8, 22, and 27 (IC(50) < 5.6 μM). The structural requirements to induce selective toxicity are discussed to shed light on the development of new anticancer drugs.