31385-19-0Relevant academic research and scientific papers
Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase
Neelakantan, Harshini,Wang, Hua-Yu,Vance, Virginia,Hommel, Jonathan D.,McHardy, Stanton F.,Watowich, Stanley J.
, p. 5015 - 5028 (2017/06/28)
Nicotinamide N-methyltransferase (NNMT) is a fundamental cytosolic biotransforming enzyme that catalyzes the N-methylation of endogenous and exogenous xenobiotics. We have identified small molecule inhibitors of NNMT with >1000-fold range of activity and developed comprehensive structure-Activity relationships (SARs) for NNMT inhibitors. Screening of N-methylated quinolinium, isoquinolinium, pyrididium, and benzimidazolium/benzothiazolium analogues resulted in the identification of quinoliniums as a promising scaffold with very low micromolar (IC50 à 1 μM) NNMT inhibition. Computer-based docking of inhibitors to the NNMT substrate (nicotinamide)-binding site produced a robust correlation between ligand-enzyme interaction docking scores and experimentally calculated IC50 values. Predicted binding orientation of the quinolinium analogues revealed selective binding to the NNMT substrate-binding site residues and essential chemical features driving protein-ligand intermolecular interactions and NNMT inhibition. The development of this new series of small molecule NNMT inhibitors direct the future design of lead drug-like inhibitors to treat several metabolic and chronic disease conditions characterized by abnormal NNMT activity.
Synthesis, spectral properties of cell-permeant dimethine cyanine dyes and their application as fluorescent probes in living cell imaging and flow cytometry
Zhang,Liu,Shi,Wang,Fu,Wei,Yang
, p. 232 - 240 (2013/10/22)
A series of dimethine cyanine dyes, used as fluorescent probes, were synthesized under microwave irradiation, and identified by 1H NMR, IR, elemental analysis and HRMS. The investigation of their spectral properties in phosphate-buffer saline (PBS) showed that the absorption and emission maxima of the dyes were in the region 370-480 nm and 471-569 nm, respectively. The properties of the dyes as fluorescent probes for living cells imaging and flow cytometry were investigated. The results showed that dyes 1, 2, 8 or 9 could penetrate an intact cell membrane, stained the cell nuclear and exhibited bright fluorescence. Little background interference, low cell cytotoxicity and little photobleaching were showed during the imaging tests. The dyes 1, 8 and 9 could be applied in flow cytometry and dye 1/PI, dye 8/PI or dye 9/PI couple could be proposed as double staining agents to measure sperm cell viability. Thus the dyes represented the cell-permeant fluorescent probes.
