6112-83-0Relevant articles and documents
Novel lithocholaphanes: Syntheses, NMR, MS, and molecular modeling studies
Valkonen, Arto,Siev?nen, Elina,Ikonen, Satu,Lukashev, Nikolai V.,Donez, Pavel A.,Averin, Alexej D.,Lahtinen, Manu,Kolehmainen, Erkki
, p. 65 - 73 (2007)
Novel head-to-head lithocholaphanes 6 and 11 have been synthesized via precursors 1-5 and 7-10 with overall good yields, and characterized by 1H, 13C, and 15N NMR spectroscopy, ESI-TOF mass spectrometry, thermal analysis,
Bile Acid Tethered Docetaxel-Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes
Sreekanth, Vedagopuram,Kar, Animesh,Kumar, Sandeep,Pal, Sanjay,Yadav, Poonam,Sharma, Yamini,Komalla, Varsha,Sharma, Harsh,Shyam, Radhey,Sharma, Ravi Datta,Mukhopadhyay, Arnab,Sengupta, Sagar,Dasgupta, Ujjaini,Bajaj, Avinash
, p. 5394 - 5399 (2021/02/05)
In this study, we describe the engineering of sub-100 nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel (DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS, DTX-PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non-rodent species including non-human primates. We further demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next-generation chemotherapeutic.
Development of novel lithocholic acid derivatives as vitamin D receptor agonists
Masuno, Hiroyuki,Kazui, Yuko,Tanatani, Aya,Fujii, Shinya,Kawachi, Emiko,Ikura, Teikichi,Ito, Nobutoshi,Yamamoto, Keiko,Kagechika, Hiroyuki
, p. 3674 - 3681 (2019/07/10)
Lithocholic acid (2) was identified as the second endogenous ligand of vitamin D receptor (VDR), though its binding affinity to VDR and its vitamin D activity are very weak compared to those of the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1). 3-Acylated lithocholic acids were reported to be slightly more potent than lithocholic acid (2) as VDR agonists. Here, aiming to develop more potent lithocholic acid derivatives, we synthesized several derivatives bearing a 3-sulfonate/carbonate or 3-amino/amide substituent, and examined their differentiation-inducing activity toward human promyelocytic leukemia HL-60 cells. Introduction of a nitrogen atom at the 3-position of lithocholic acid (2) decreased the activity, but compound 6 bearing a 3-methylsulfonate group showed more potent activity than lithocholic acid (2) or its acylated derivatives. The binding of 6 to VDR was confirmed by competitive binding assay and X-ray crystallographic analysis of the complex of VDR ligand-binding domain (LBD) with 6.
snorkelling : Vs. diving in mixed micelles probed by means of a molecular bathymeter
Rodriguez-Mu?iz, Gemma M.,Gomez-Mendoza, Miguel,Nuin, Edurne,Andreu, Inmaculada,Marin, M. Luisa,Miranda, Miguel A.
, p. 10281 - 10288 (2017/12/26)
A photoactive bathymeter based on a carboxylic acid moiety covalently linked to a signalling methoxynaphthalene (MNP) fluorophore has been designed to prove the concept of snorkelling vs. diving in mixed micelles (MM). The carboxylic acid floats on the MM surface, while the MNP unit sinks deep in MM. The rate constants of MNP fluorescence quenching by iodide, which remains basically in water, consistently decrease with increasing spacer length, revealing different regions. This is associated with the distance MNP should dive in MM to achieve protection from aqueous reactants. Unequivocal proof of the exergonic photoinduced electron transfer was obtained from the UV-visible spectral signature of I3- upon steady-state photolysis. The applicability of the bathymeter was examined upon testing a family of MNP derivatives. The obtained results were validated by comparison with different lipophilicity tests: (i) a modified version of the Kow partition coefficient and (ii) the retention factor on thin layer chromatography. This concept could potentially be extended to test drugs or pharmacophores exhibiting any photoactive moiety.
