33628-48-7Relevant articles and documents
Design and synthesis of novel chiral dendritic species derived from bile acids
Balasubramanian,Maitra
, p. 3035 - 3040 (2001)
Bile acids have been used for the first time as the building block for the construction of dendritic units. Orthogonally functionalized 7-deoxycholic and cholic acid derivatives were synthesized. The construction of a bile acid heptamer, a nonamer, and a decamer using the convergent strategy are described in detail. Chromatographic, spectral, and optical properties of these molecules have been investigated. Molecular modeling suggests that these molecules have globular shapes with nanometric dimensions.
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).
Novel semisynthetic derivatives of bile acids as effective tyrosyl-DNA phosphodiesterase 1 inhibitors
Salomatina, Oksana V.,Popadyuk, Irina I.,Zakharenko, Alexandra L.,Zakharova, Olga D.,Fadeev, Dmitriy S.,Komarova, Nina I.,Reynisson, Jóhannes,Arabshahi, H. John,Chand, Raina,Volcho, Konstantin P.,Salakhutdinov, Nariman F.,Lavrik, Olga I.
, (2018)
An Important task in the treatment of oncological and neurodegenerative diseases is the search for new inhibitors of DNA repair system enzymes. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the DNA repair system enzymes involved in the removal of DNA damages caused by topoisomerase I inhibitors. Thus, reducing the activity of Tdp1 can increase the effectiveness of currently used anticancer drugs. We describe here a new class of semisynthetic small molecule Tdp1 inhibitors based on the bile acid scaffold that were originally identified by virtual screening. The influence of functional groups of bile acids (hydroxy and acetoxy groups in the steroid framework and amide fragment in the side chain) on inhibitory activity was investigated. In vitro studies demonstrate the ability of the semisynthetic derivatives to effectively inhibit Tdp1 with IC50 up to 0.29 μM. Furthermore, an excellent fit is realized for the ligands when docked into the active site of the Tdp1 enzyme.
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.
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi
García Li?ares, Guadalupe,Antonela Zígolo,Simonetti, Leandro,Longhi, Silvia A.,Baldessari, Alicia
, p. 4804 - 4814 (2015)
Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8 μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents.
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.
Phenylbutazone, a New Long-Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier
Zhou, Jie,Li, Xue,Zhu, Xiaoyun,Sun, Jian,Qiu, Qianqian,Huang, Wenlong,Qian, Hai
, p. 936 - 945 (2016)
As a NPY-2 receptor agonist, PYY24-36-Leu31 is reported to suppress appetite and has a potential in obesity treatment, but its short half-life limits the clinical application. The use of chemical modification to improve interactions
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
Synthesis of 24-phenyl-24-oxo steroids derived from bile acids by palladium-catalyzed cross coupling with phenylboronic acid. NMR characterization and X-ray structures
Mayorquin-Torres, Martha C.,Romero-Avila, Margarita,Flores-Alamo, Marcos,Iglesias-Arteaga, Martin A.
, p. 1092 - 1097 (2013)
Palladium-catalyzed cross coupling of phenyboronic acid with acetylated bile acids in which the carboxyl functions have been activated by formation of a mixed anhydride with pivalic anhydride afforded moderate to good yield of 24-phenyl-24-oxo-steroids. U
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.
