150-96-9Relevant articles and documents
Synthesis and antitumour activity of β-hydroxyisovalerylshikonin analogues
Rao, Zhen,Liu, Xin,Zhou, Wen,Yi, Jing,Li, Shao-Shun
experimental part, p. 3934 - 3941 (2011/11/12)
A series of novel β-hydroxyisovalerylshikonin analogues bearing oxygen-containing substituents at the side-chain hydroxyl of shikonin were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against multi-drug resistant (MDR) cell lines DU-145 and HeLa. Most compounds exhibited significant inhibitory activity on both cell lines. The structure-activity relationship showed the analogues with ether substituents displayed the most potent antitumour activity and selective cytotoxicity towards DU-145. Among the compounds with ether substituents, increasing the steric hindrance in the carbon bearing β-hydroxyl or replace the β-hydroxyl with acetoxy or methoxy would lead to the decline of cytotoxicity.
Structural characterization of substrates for the anion exchange transporter in Caco-2 cells
Ogihara, Takuo,Tamai, Ikumi,Tsuji, Akira
, p. 1217 - 1221 (2007/10/03)
The present study was conducted to characterize the structural specificity of an anion exchange transporter in intestinal epithelial cells. The transport of carboxylic acids with hydroxyl group(s) at the 2, 3, 4, and/or 5 positions with respect to carboxylate was examined by using Caco-2 cells in the presence of bicarbonate ions on the basolateral side to enhance the activity of the anion-exchange transporter. In the presence of the bicarbonate ion gradient, transport of L-lactic acid consisted of a saturable process and a nonsaturable process as judged from the Eadie-Hofstee plot. The transport of L-lactic acid at 1 μM was reduced by sodium azide, dinitrophenol, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was also reduced by 2-, 4-, and 5-hydroxycarboxylic acids such as hydroxyacetic acid, 4-hydroxybutyric acid, and 5-hydroxydecanoic acid, but not by 3-hydroxycarboxylic acids such as 3-hydroxypropionic acid and 3- hydroxybutyric acid. Transport of both 2- and 4-hydroxybutyric acids involved saturable and nonsaturable processes, whereas that of 3-hydroxybutyric acid was nonsaturable and was not inhibited by DIDS. These results indicate that 3-hydroxycarboxylic acids might not be substrates for this anion exchange transporter in intestinal epithelial cells, suggesting that the position of hydroxylation is significant for molecular recognition by the transporter.
Enantioselective Hydrolysis of 3-Hydroxy-3-methylalkanoic Acid Esters with Pig Liver Esterase
Wilson, William K.,Baca, Shawn B.,Barber, Yolanda J.,Scallen, Terence J.,Morrow, Cary J.
, p. 3960 - 3966 (2007/10/02)
Pig liver esterase has been shown to stereoselectively hydrolyze the R enantiomer of several chiral 3-hydroxy-3-methylalkanoic acid esters of the form RC(Me)(OH)CH2COOR', where R = Et, CH2=CHCH2, Me(CH2)5, (MeO)2CHCH2, and PhCH2OCH2CH2 and R'= Me or Et.The unhydrolyzed ester and the reesterified carboxylic acid were analyzed for enantiomeric purity by NMR using the chiral shift reagent Eu(hfc)3.For the compounds studied, the S enantiomers consistently showed greater induced shifts.Products of the resolution are potential intermediates in the preparation of compactin analogues having defined stereochemistry at carbon-3.These analogues will be useful in testing the hypothesis that the hypocholesterolemic activity of compactin and its analogues resides in their ability to mimic the binding of mevaldic acid coenzyme A hemithioacetal to HMG-CoA reductase but not be reduced to mevalonate.