Synthesis and anti–tumour, immunomodulating activity of diosgenin and tigogenin conjugates

Publication date: Available online 1 February 2020Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): O. Michalak, P. Krzeczyński, M. Cieślak, P. Cmoch, M. Cybulski, K. Królewska-Golińska, J. Kaźmierczak-Barańska, B. Trzaskowski, K. OstrowskaAbstractA series of novel diosgenin (DSG) and tigogenin (TGG) derivatives with diosgenin or tigogenin steroid aglycons linked to levulinic and 3,4–dihydroxycinnamic acids, dipeptides and various amino acids by an ester bond at the C3–oxygen atom of the steroid skeleton has been synthesized. Diosgenyl esters have been prepared by an esterification reaction (DCC/DMAP) of diosgenin with the corresponding acids.All analogues have been evaluated in vitro for their antiproliferative profile against cancer cell lines (MCF–7, MDA–MB–231, PC–3) and human umbilical vein endothelial cells (HUVEC). Analogue 2c (l–serine derivative of TGG), the best representative of the series showed IC50 of 1.5 µM (MCF–7), and induced apoptosis in MCF–7 by activating caspase–3/7.The immunomodulatory properties of six synthesized analogues have been determined by examining their effects on the expression of cytokine genes essential for the functioning of the human immune system (IL–1, IL–4, IL–10, IL–12 and TNF–α). Biological evaluation has revealed that new compounds 4c and 16a do not induce the expression of pro–inflammatory cytokines in THP–1 cells after the lipopolysaccharide (LPS) stimulation. The...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research