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 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.