Synthesis and characterization of organometallic rhenium(І) and technetium(І) bile acid complexes

Huang, Liliang; Zhu, Hua; Xu, Xiaoping; Zhang, Chunchun; Shen, Yu‐Mei

doi:10.1016/j.jorganchem.2009.06.015

Cited by 12 publications

(3 citation statements)

References 34 publications

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“…The synthesis of oxysterols was started with commercially available hyodeoxycholic acid (UHN Shanghai Research and Development Co., Ltd. Shanghai, China ). The esterification of hyodeoxycholic acid afforded the corresponding methyl hyodeoxycholate, which reacted with tosyl chloride in pyridine to yield the ditosylated ester, methyl 3α, 7β-ditosyloxy-5β-cholan-24-oate [ 68 , 69 ]. Next, in the presence of acetic acid (AcOK) by using N,N-Dimethylformamide (DMF)/H2O as a solvent, alkene methyl 3β-hydroxychol-5-en-24-oate ( S1 ) was obtained in 50.9% yield from methyl 3α, 7β-ditosyloxy-5β-cholan-24-oate via S N 2 displacement and elimination, together with large quantities of acetylated 3β-formyloxychola-5-ene-24-oic acid methyl ester ( S2 ) or 3β-acetoxychola-5-ene-24-oic acid methyl ester ( S3 ) ( Figure 8 .…”

Section: Methodsmentioning

confidence: 99%

Identification of Side Chain Oxidized Sterols as Novel Liver X Receptor Agonists with Therapeutic Potential in the Treatment of Cardiovascular and Neurodegenerative Diseases

Zhan

Wang

Martens

et al. 2023

IJMS

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The nuclear receptors—liver X receptors (LXR α and β) are potential therapeutic targets in cardiovascular and neurodegenerative diseases because of their key role in the regulation of lipid homeostasis and inflammatory processes. Specific oxy(phyto)sterols differentially modulate the transcriptional activity of LXRs providing opportunities to develop compounds with improved therapeutic characteristics. We isolated oxyphytosterols from Sargassum fusiforme and synthesized sidechain oxidized sterol derivatives. Five 24-oxidized sterols demonstrated a high potency for LXRα/β activation in luciferase reporter assays and induction of LXR-target genes APOE, ABCA1 and ABCG1 involved in cellular cholesterol turnover in cultured cells: methyl 3β-hydroxychol-5-en-24-oate (S1), methyl (3β)-3-aldehydeoxychol-5-en-24-oate (S2), 24-ketocholesterol (S6), (3β,22E)-3-hydroxycholesta-5,22-dien-24-one (N10) and fucosterol-24,28 epoxide (N12). These compounds induced SREBF1 but not SREBP1c-mediated lipogenic genes such as SCD1, ACACA and FASN in HepG2 cells or astrocytoma cells. Moreover, S2 and S6 enhanced cholesterol efflux from HepG2 cells. All five oxysterols induced production of the endogenous LXR agonists 24(S)-hydroxycholesterol by upregulating the CYP46A1, encoding the enzyme converting cholesterol into 24(S)-hydroxycholesterol; S1 and S6 may also act via the upregulation of desmosterol production. Thus, we identified five novel LXR-activating 24-oxidized sterols with a potential for therapeutic applications in neurodegenerative and cardiovascular diseases.

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Section: Methodsmentioning

confidence: 99%

Identification of Side Chain Oxidized Sterols as Novel Liver X Receptor Agonists with Therapeutic Potential in the Treatment of Cardiovascular and Neurodegenerative Diseases

Zhan

Wang

Martens

et al. 2023

IJMS

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“…More recent variations of established 99m Tc-IDAs include carbonyl ligands [161]. Another approach is to exploit the imaging potential of bile acids, since these are natural ligands recognized by the liver [162]. Thus far, attempts have focused on 99m Tc and 111 In complexes of bile acid conjugates, which have shown hepatobiliary uptake and excretion [162,163].…”

Section: Metal Complexes In Scintigraphic Liver Imagingmentioning

confidence: 99%

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

2019

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This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy and positron emission tomography (PET). The review provides an overview on approved pharmaceuticals like Gd-based CA and 99mTc-based radiometal complexes, and also on novel agents such as 68Ga-based PET tracers. Metal complexes are presented by their imaging modality, with subsections focusing on their structure and mode of action. Uptake mechanisms, metabolism, and specificity are presented, in context with advantages and limitations of the diagnostic application and taking into account the respective imaging technique.

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“…Bile acids were also used as bioligands for coordination to group 7 metals (Scheme ) in order to explore diagnosis applications in the field of hepatobiliary diseases along with intestinal and liver cancers . Thus, cholic acid 185a , chenodeoxycholic acid 185b , ursodeoxycholic acid 185c , and hyodeoxycholic acid 185d were transformed via a three-step procedure (esterification, amination, and reductive amination) into the corresponding tridentate ligands 186a – d and 187a – d with reasonable yields.…”

Section: Potential Radiopharmaceuticalsmentioning

confidence: 99%