Malyarenko TV et al. (2020), New Conjugates of Polyhydroxysteroids with Long...

ECB-ART-49821

Mar Drugs 2020 May 15;185:. doi: 10.3390/md18050260.

Show Gene links Show Anatomy links

New Conjugates of Polyhydroxysteroids with Long-Chain Fatty Acids from the Deep-Water Far Eastern Starfish Ceramaster patagonicus and Their Anticancer Activity.

Malyarenko TV , Kicha AA , Malyarenko OS , Zakharenko VM , Kotlyarov IP , Kalinovsky AI , Popov RS , Svetashev VI , Ivanchina NV .

???displayArticle.abstract???
Four new conjugates, esters of polyhydroxysteroids with long-chain fatty acids (1-4), were isolated from the deep-water Far Eastern starfish Ceramaster patagonicus. The structures of 1-4 were established by NMR and ESIMS techniques as well as chemical transformations. Unusual compounds 1-4 contain the same 5α-cholestane-3β,6β,15α,16β,26-pentahydroxysteroidal moiety and differ from each other in the fatty acid units: 5'Z,11'Z-octadecadienoic (1), 11'Z-octadecenoic (2), 5'Z,11'Z-eicosadienoic (3), and 7'Z-eicosenoic (4) acids. Previously, only one such steroid conjugate with a fatty acid was known from starfish. After 72 h of cell incubation, using MTS assay it was found that the concentrations of compounds 1, 2, and 3 that caused 50% inhibition of growth (IC50) of JB6 Cl41 cells were 81, 40, and 79 µM, respectively; for MDA-MB-231 cells, IC50 of compounds 1, 2, and 3 were 74, 33, and 73 µM, respectively; for HCT 116 cells, IC50 of compounds 1, 2, and 3 were 73, 31, and 71 µM, respectively. Compound 4 was non-toxic against tested cell lines even in three days of treatment. Compound 2 (20 µM) suppressed colony formation and migration of MDA-MB-231 and HCT 116 cells.

???displayArticle.pubmedLink??? 32429281
???displayArticle.pmcLink??? PMC7281419
???displayArticle.link??? Mar Drugs
???displayArticle.grants??? [+]

???attribute.lit??? ???displayArticles.show???

	Figure 1. The structures of compounds 1–4 isolated from C. patagonicus.
	Figure 2. (A) 1H-1H COSY and key HMBC correlations for compound 1. (B) Key ROESY correlations of steroidal moiety for compounds 1–4.
	Figure 3. The cytostatic activity of compounds 1–4 against normal epidermal JB6 Cl41 cells, breast cancer MDA-MB-231 cells, and colorectal carcinoma HCT 116 cells. (A) JB6 Cl41, (B) MDA-MB-231, or (C) HCT 116 cells were treated with compounds 1–4 at concentrations of 1–100 µM for 24, 48, and 72 h. Cell viability was estimated using the MTS assay. Data are represented as the mean ± SD as determined from triplicate experiments.
	Figure 4. The effect of compounds 1–4 on colony formation in human cancer cells. MDA-MB-231 (A) or HCT 116 cells (B) (2.4 × 104) were treated with or without investigated compounds (20 µM) and applied onto 0.3% Basal Medium Eagle (BME) agar containing 10% FBS, 2 mM L-glutamine, and 25 µg/mL gentamicin. After 14 days of incubation, the number of colonies was evaluated under a microscope with the aid of the ImageJ software program. Results are expressed as the mean ± standard deviation (SD). The asterisks ( p < 0.01, * p < 0.001) indicate a significant decrease in colony number of cancer cells treated by compounds compared with control.
	Figure 5. The effect of compounds 1–4 on migration of human cancer cells. MDA-MB-231 (A,B) and HCT 116 (C,D) cells migration distance was estimated by measuring the width of the wound and expressed as a percentage of each control for the mean of wound closure area. All experiments were repeated at least three times in each group (n = 18 for control and each compound, n—quantity of photos). The magnification of representative photos is ×10. Results are expressed as the mean ± standard deviation (SD). The asterisks (* p < 0.05, p < 0.01, * p < 0.001) indicate a significant decrease in migration of cells treated with compounds compared with the control.

References [+] :

Borowicz, The soft agar colony formation assay. 2014, Pubmed