33628-48-7Relevant articles and documents
First bile acid-derived chiral dendritic species with nanometric dimensions
Balasubramanian,Rao, Photon,Maitra
, p. 2353 - 2354 (1999)
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Bile Acid Derivatives of 5-Amino-1,3,4-thiadiazole-2-sulfonamide as New Carbonic Anhydrase Inhibitors: Synthesis and Investigation of Inhibition Effects
Buelbuel, Metin,Saracoglu, Nurullah,Kuefrevioglu, Oe. Irfan,Ciftci, Mehmet
, p. 2561 - 2568 (2002)
Bile acid amides (cholan-24-amides) of 5-substituted 1,3,4-thiadiazole-2-sulfonamide have been prepared from lithocholic, deoxycholic, cholic and dehydrocholic acids. Besides, the alcohol functional groups on the cholane ring systems were protected with acetyl group. Amides of the protected cholanes of lithocholic and cholic acids were also synthesized. Later, inhibition effects of these compounds on human carbonic anhydrase isozymes (HCA-I and II) have been investigated in vitro. For the most active compounds, inhibition constants ranged from 66 to 190 nM for HCA-II with I50 (molarity of inhibitor producing a 50 percent inhibition of CA activity). In addition, in vivo studies were performed for the synthesized compounds in Sprague-Dawley rats. The compounds (11 and 18) showed especially significant inhibition efficacy (p 0.001).
Synthesis of cyclocholates and derivatives
Gao, Hongwu,Dias, Jerry Ray
, p. 757 - 776 (1997)
A synthesis of bile acid cyclooligomers by the Yamaguchi method is described. Cyclotrimerization is the principal reaction route for te cholic acid system, and cyclotetramerization is the principal reaction route for the 24-norcholic acid.
Structure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities
Leverrier, Aurélie,Bero, Joanne,Cabrera, Julián,Frédérich, Michel,Quetin-Leclercq, Jo?lle,Palermo, Jorge A.
, p. 10 - 17 (2015)
In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids were prepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a covalent C-C bond via a decarboxylative Barton-Zard reaction between the two entities. The bile acids showed only weak antiparasitic properties, but all the hybrids exhibited high in vitro activities (IC50: 0.48-5.39 μM) against Trypanosoma brucei. These hybrids were more active than their respective parent alkaloids (up to a 135 fold increase in activity), and displayed good selectivity indices. Aditionally, all these compounds inhibited the in vitro growth of a chloroquine-sensitive strain of Plasmodium falciparum (3D7: IC50: 36.1 nM to 8.72 μM), and the most active hybrids had IC50s comparable to that of artemisinin (IC50: 36 nM). Some structure-activity relationships among the group of 48 hybrids are discussed. The increase in antiparasitic activity may be explained by an improvement in bioavailability, since the more lipophilic derivatives showed the lowest IC50s.
Calix[4]arene-cholic acid conjugates: A new class of efficient synthetic ionophores
Maulucci, Nakia,De Riccardis, Francesco,Botta, Cinzia Barbara,Casapullo, Agostino,Cressina, Elena,Fregonese, Massimo,Tecilla, Paolo,Izzo, Irene
, p. 1354 - 1356 (2005)
The synthesis of a new class of amphiphilic calix[4]arene-based ionophores, relying on direct reductive amination as a key step, and the evaluation of their H+and Na+transporting properties is described. The Royal Society of Chemistr
Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis
Cao, Jing,Cheng, Aolin,Liu, Tao,Song, Guanshui,Zhang, Kun,Zhang, Liangliang,Zhao, Baoguo,Zhao, Guoqing,Zhou, Qinghai
supporting information, p. 20166 - 20172 (2021/07/20)
The direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β-hydroxy-α-amino-acid derivatives. But it is not easy to realize the transformation due to the disruption of the reactive NH2 group of glycinates. Inspired by the enzymatic aldol reaction of glycine, we successfully developed an asymmetric aldol reaction of glycinate 5 and trifluoromethyl ketones 4 with 0.1–0.0033 mol % of chiral N-methyl pyridoxal 7 a as the catalyst, producing chiral β-trifluoromethyl-β-hydroxy-α-amino-acid esters 6 in 55–82 % yields (for the syn-diastereomers) with up to >20:1 dr and 99 % ee under very mild conditions. The reaction proceeds via a catalytic cycle similar to the enzymatic aldol reaction of glycine. Pyridoxal catalyst 7 a activates both reactants at the same time and brings them together in a specific spatial orientation, accounting for the high efficiency as well as excellent diastereo- and enantioselectivities.
Leveraging of rifampicin-dosed cynomolgus monkeys to identify bile acid 3-O-sulfate conjugates as potential novel biomarkers for organic anion-transporting polypeptidess
Thakare, Rhishikesh,Gao, Hongying,Kosa, Rachel E.,Bi, Yi-An,Varma, Manthena V. S.,Cerny, Matthew A.,Sharma, Raman,Kuhn, Max,Huang, Bingshou,Liu, Yiping,Yu, Aijia,Walker, Gregory S.,Niosi, Mark,Tremaine, Larry,Alnouti, Yazen,Rodrigues, A. David
supporting information, p. 721 - 733 (2017/06/27)
In the search for novel bile acid (BA) biomarkers of liver organic anion-transporting polypeptides (OATPs), cynomolgus monkeys received oral rifampicin (RIF) at four dose levels (1, 3, 10, and 30 mg/kg) that generated plasma-free Cmax values (0.06, 0.66, 2.57, and 7.79 μM, respectively) spanning the reported in vitro IC50 values for OATP1B1 and OATP1B3 (≤1.7 μM). As expected, the area under the plasma concentration-time curve (AUC) of an OATP probe drug (i.v.2H4-pitavastatin, 0.2 mg/kg) was increased 1.2-, 2.4-, 3.8-, and 4.5-fold, respectively. Plasma of RIF-dosed cynomolgus monkeys was subjected to a liquid chromatography-tandem mass spectrometry method that supported the analysis of 30 different BAs. Monkey urine was profiled, and we also determined that the impact of RIF on BA renal clearance was minimal. Although sulfated BAs comprised only 1% of the plasma BA pool, a robust RIF dose response (maximal ?50-fold increase in plasma AUC) was observed for the sulfates of five BAs [glycodeoxycholate (GDCA-S), glycochenodeoxycholate (GCDCA-S), taurochenodeoxycholate, deoxycholate (DCA-S), and taurodeoxycholate (TDCA-S)]. In vitro, RIF (≤100 μM) did not inhibit cynomolgus monkey liver cytosol-catalyzed BA sulfation and cynomolgus monkey hepatocyte-mediated uptake of representative sulfated BAs (GDCA-S, GCDCA-S, DCA-S, and TDCA-S) was sodium-independent and inhibited (≥70%) by RIF (5 μM); uptake of taurocholic acid was sensitive to sodium removal (74% decrease) and relatively refractory to RIF (≤21% inhibition). We concluded that sulfated BAs may serve as sensitive biomarkers of cynomolgus monkey OATPs and that exploration of their utility as circulating human OATP biomarkers is warranted.
