2483-51-4Relevant articles and documents
HIGH OXIDATION STATE TRANSITION METAL CARBOXYLATES AS ACYLATING AGENTS
Recht, Joel,Cohen, Brett I.,Goldman, Alan S.,Kohn, Joachim
, p. 7281 - 7284 (1990)
The formation of amide bonds from the reaction of metal carboxylates with amines was observed for the first time; complexes for titanium(IV), zirconium(IV) and tantalum(V) were investigated.
Optimization and anti-cancer properties of fluoromethylketones as covalent inhibitors for ubiquitin C-terminal hydrolase L1
Chen, Hao,Das, Chittaranjan,Flaherty, Daniel P.,Galardy, Paul J.,Hewitt, Chad S.,Hussain, Sajjad,Imhoff, Ryan D.,Krabill, Aaron D.,Muli, Christine S.,Wendt, Michael K.
, (2021/05/31)
The deubiquitinating enzyme (DUB) UCHL1 is implicated in various disease states including neurodegenerative disease and cancer. However, there is a lack of quality probe molecules to gain a better understanding on UCHL1 biology. To this end a study was carried out to fully characterize and optimize the irreversible covalent UCHL1 inhibitor VAEFMK. Structure-activity relationship studies identified modifications to improve activity versus the target and a full cellular characterization was carried out for the first time with this scaffold. The studies produced a new inhibitor, 34, with an IC50 value of 7.7 μM against UCHL1 and no observable activity versus the closest related DUB UCHL3. The molecule was also capable of selectively inhibiting UCHL1 in cells and did not demonstrate any discernible off-target toxicity. Finally, the molecule was used for initial probe studies to assess the role of UCHL1 role in proliferation of myeloma cells and migration behavior in small cell lung cancer cells making 34 a new tool to be used in the biological evaluation of UCHL1.
Investigation of permeation of theophylline through skin using selected piperazine-2,5-diones
Pokorna, Aneta,Bobal, Pavel,Oravec, Michal,Rarova, Lucie,Bobalova, Janette,Jampilek, Josef
, (2019/02/26)
Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 ?C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.
