78793-10-9Relevant articles and documents
Characterization of novel fluorescent bile salt derivatives for studying human bile salt and organic anion transporters
Euler, Adriana,Leuenberger, Michele,Lochner, Martin,Stieger, Bruno,H?usler, Stephanie,H?hn, Vera
, p. 346 - 357 (2021/06/08)
Bile salts, such as cholate, glycocholate, taurocholate, and glycochenodeoxycholate, are taken up from the portal blood into hepatocytes via transporters, such as the Na+-taurocholate–cotransporting polypeptide (NTCP) and organic anion–transporting polypeptides (OATPs). These bile salts are later secreted into bile across the canalicular membrane, which is facilitated by the bile salt export pump (BSEP). Apart from bile salt transport, some of these proteins (e.g., OATPs) are also key transporters for drug uptake into hepatocytes. In vivo studies of transporter function in patients by using tracer compounds have emerged as an important diagnostic tool to complement classic liver parameter measurements by determining dynamic liver function both for diagnosis and monitoring progression or improvement of liver diseases. Such approaches include use of radioactively labeled bile salts (e.g., for positron emission tomography) and fluorescent bile salt derivatives or dyes (e.g., indocyanine green). To expand the list of liver function markers, we synthesized fluorescent derivatives of cholic and chenodeoxycholic acid by conjugating small organic dyes to the bile acid side chain. These novel fluorescent probes were able to block substrate transport in a concentration-dependent manner of NTCP, OATP1B1, OATP1B3, OATP2B1, BSEP, and intestinal apical sodium-dependent bile salt transporter (ASBT). Whereas the fluorescent bile acid derivatives themselves were transported across the membrane by OATP1B1, OATP1B3, and OATP2B1, they were not transport substrates for NTCP, ASBT, BSEP, and multidrug resistance-related protein 2. Accordingly, these novel fluorescent bile acid probes can potentially be used as imaging agents to monitor the function of OATPs. SIGNIFICANCE STATEMENT Synthetic modification of common bile acids by attachment of small organic fluorescent dyes to the bile acid side chain resulted in bright, fluorescent probes that interact with hepatic and intestinal organic anion [organic anion–transporting polypeptide (OATP) 1B1, OATP1B3, OATP2B1], bile salt uptake (Na+-taurocholate–cotransporting polypeptide, apical sodium-dependent bile salt transporter), and bile salt efflux (bile salt export pump, multidrug resistance-related protein 2) transporters. Although the fluorescent bile salt derivatives are taken up into cells via the OATPs, the efflux transporters do not transport any of them but one.
Synthesis and characterization of organometallic rhenium(I{cyrillic, ukrainian}) and technetium(I{cyrillic, ukrainian}) bile acid complexes
Huang, Liliang,Zhu, Hua,Xu, Xiaoping,Zhang, Chunchun,Shen, Yu-Mei
experimental part, p. 3247 - 3253 (2010/01/11)
Eight bile acid derivatives have been synthesized with alkyl chains of various length based tridentate ligand chelating system. These derivatives have been reacted with the precursor [Et4N]2[Re(CO)3Br3] and fac-[M(CO)3(H2O)3]+ (M = 99mTc, Re) in ethanol or ethanol-aqueous media to form water-soluble and stable organometallic complexes in good yields. 1H NMR, 13C NMR, IR and elemental analysis or HRMS spectroscopic analyses confirmed the tridentate complexation of the metal-tricarbonyl fragment exclusively via the tridentate chelates. In addition, the corresponding radioactive technetium-99m complexes were prepared successfully and challenged for stability in physiological phosphate buffer at 37 °C for 24 h. No decomposition of the complexes could be detected under the condition proving the stability of these complexes.
