41993-79-7Relevant academic research and scientific papers
Hydroxylated Rotenoids Selectively Inhibit the Proliferation of Prostate Cancer Cells
Russell, David A.,Bridges, Hannah R.,Serreli, Riccardo,Kidd, Sarah L.,Mateu, Natalia,Osberger, Thomas J.,Sore, Hannah F.,Hirst, Judy,Spring, David R.
, p. 1829 - 1845 (2020/06/05)
Prostate cancer is one of the leading causes of cancer-related death in men. The identification of new therapeutics to selectively target prostate cancer cells is therefore vital. Recently, the rotenoids rotenone (1) and deguelin (2) were reported to selectively kill prostate cancer cells, and the inhibition of mitochondrial complex I was established as essential to their mechanism of action. However, these hydrophobic rotenoids readily cross the blood-brain barrier and induce symptoms characteristic of Parkinson's disease in animals. Since hydroxylated derivatives of 1 and 2 are more hydrophilic and less likely to readily cross the blood-brain barrier, 29 natural and unnatural hydroxylated derivatives of 1 and 2 were synthesized for evaluation. The inhibitory potency (IC50) of each derivative against complex I was measured, and its hydrophobicity (Slog10P) predicted. Amorphigenin (3), dalpanol (4), dihydroamorphigenin (5), and amorphigenol (6) were selected and evaluated in cell-based assays using C4-2 and C4-2B prostate cancer cells alongside control PNT2 prostate cells. These rotenoids inhibit complex I in cells, decrease oxygen consumption, and selectively inhibit the proliferation of prostate cancer cells, leaving control cells unaffected. The greatest selectivity and antiproliferative effects were observed with 3 and 5. The data highlight these molecules as promising therapeutic candidates for further evaluation in prostate cancer models.
Synthesis of the Pyranoisoflavonoid, Heminitidulan. Isoflavanoid and Rotenoid Glycosides from the Bark of Dalbergia nitidula Welw. ex Bak.
Heerden, Fanie R. van,Brandt, E. Vincent,Roux, David G.
, p. 2463 - 2469 (2007/10/02)
Synthesis of racemates of the complex pyranoisoflavan, (3S)-heminitidulan, a metabolite from the bark of Dalbergia nitidula, is accomplished.The isoflavone C-glycoside pairs 8-C-β-D-glucopyranosyl- and 6,8-di-C-β-glucopyranosyl-genistein and -orobol and the associated rotenoid glycoside (5'R,6aR,12aR)-8'-O-β-D-glucopyranosyl-12a-hydroxyamorphigenin comprise the predominant isoflavonoids in the same source. 13C N.m.r. spectra of the glycosides are recorded.
