Synthesis and cytotoxic evaluation of four new 6E-hydroximinosteroids

• Published in: Steroids 2014-06, Vol.84, p.7-10
• Main Authors: Richmond, Victoria, Careaga, Valeria P., Sacca, Paula, Calvo, Juan C., Maier, Marta S.
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Hydroximinosteroids; Male; Prostate cancer; Proton Magnetic Resonance Spectroscopy; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Steroids - chemical synthesis; Steroids - pharmacology; Sulfated steroids; Synthesis
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2014.03.001

[Display omitted] •6E-hydroximinosteroids were synthesized from the corresponding ketones.•Cytotoxic activity of the compounds was evaluated against PC-3 and LNCaP.•The biological activity was compared to that of sulfated polyhydroxysteroid analogs.•2β,3α,6β-sulfated steroid showed the highest cytotoxicity against LNCaP. Four new 6E-hydroximinosteroids (1, 2a, 3 and 4) have been synthesized from the corresponding ketones, 2β,3β-dihydroxy-5α-cholestan-6-one (5), 2α,3α-dihydroxy-5α-cholestan-6-one (6), 2β,3α-dihydroxy-5α-cholestan-6-one (7) and 2β,3α-dihydroxy-5α-cholestan-6-one-disulfate (8). The cytotoxic activity of the steroidal oximes was evaluated against two prostate carcinoma cell lines (PC-3 and LNCaP) and compared with that of five polyhydroxylated sulfated analogs (8–12). Oxime 3 and trisulfated analog 11 were the most active compounds with IC50 values of 10.8μM (PC-3) and 7.9μM (LNCaP), respectively.