360789-59-9Relevant academic research and scientific papers
Small-molecule inhibitors of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1): Synthesis and biological evaluation
Ferla, Salvatore,Aboraia, Ahmed S.,Brancale, Andrea,Pepper, Christopher J.,Zhu, Jinge,Ochalek, Justin T.,Deluca, Hector F.,Simons, Claire
, p. 7702 - 7715 (2015/01/08)
The synthesis of imidazole styrylbenzamide, tert-butyl styrylimidazole, and tert-butyl styrylsulfonate derivatives is described. Evaluation of binding affinity and inhibitory activity against CYP24A1 identified the imidazole styrylbenzamides as potent inhibitors of CYP24A1, having selectivity with respect to CYP27B1 comparable with or greater than that of the standard ketoconazole. Further evaluation of the 3,5-dimethoxy and 3,4,5-trimethoxy derivatives in chronic lymphocytic leukemia cells revealed that co-treatment of 1α,25-dihydroxyvitamin D3plus inhibitor coordinately upregulated GADD45α and CDKN1A. Docking experiments on the inhibitors in the CYP24A1 enzyme active site suggest the compounds reach the active site through the vitamin D access tunnel and are exposed to multiple hydrophobic residues. The imidazole styrylbenzamides are optimally positioned to allow interaction of the imidazole with the heme, and, in the case of the methoxy derivatives, a hydrogen bond between the 3-methoxy group and Gln82 stabilizes the molecule in a favorable active conformation.
5′-Tethered Stilbene Derivatives as Fidelity- and Affinity-Enhancing Modulators of DNA Duplex Stability
Dogan, Zeynep,Paulini, Ralph,Stuetz, Jan A. Rojas,Narayanan, Sukunath,Richert, Clemens
, p. 4762 - 4763 (2007/10/03)
A series of 5′-linked stilbene-DNA conjugates with different substituents in the distal aromatic ring of the stilbene was prepared, and the effect of the modifications on duplex stability was determined via UV-melting curves. A trimethoxystilbene derivative as a 5′-substituent increases duplex melting points by up to 12.2 °C per modification. With this alkoxystilbene substituent, terminal mismatches in DNA duplexes lower the melting point by up to 23.4 °C over the perfectly matched control, whereas terminal mismatches in unmodified DNA cause melting point depressions of no more than 6.1 °C. An aminomethylstilbene substituent linked to an oligopyrrolamide minor groove binder increases the melting point of an all-A/T decamer by up to 32.7 °C, thus shifting the melting point into a range typical for duplexes with statistical G/C-content. An affinity- and selectivity-enhancing effect was also observed when the trimethoxystilbene cap was employed on a small DNA microarray. The phosphoramidite of the trimethoxystilbene can be readily employed in automatic DNA synthesis, facilitating the generation of DNA chips with improved fidelity. Copyright
Luminescent supramolecular assemblies based on hydrogen-bonded complexes of stilbenecarboxylic acids and dithieno[3,2-b:2′,3′-d]thiophene-2-carboxylic acids with a tris(imidazoline) base
Osterod,Peters,Kraft,Sano,Morrison,Feeder,Holmes
, p. 1625 - 1633 (2007/10/03)
The synthesis of a number of stilbenecarboxylic acids, tetrazolylstilbenes and dithieno[3,2-b:2′,3′-d]thiophene-2-carboxylic acids is reported. These organic acids form non-covalent complexes with an imidazoline base, 1,3,5-tris(4,5-dihydroimidazol-2-yl)benzene 13. Two X-ray crystal structures confirm hydrogen bonds between carboxylate ligands and meta-positioned protonated imidazoline groups. The complexes possess a surprisingly flat disk-like shape with various close contacts between adjacent molecules. Most stilbene and dithieno[3,2-b:2′,3′-d]thiophene derivatives show strong blue or blue-green photoluminescence in solution, whereas fluorescence in the solid state is almost completely quenched.
