1.Acyl-based anandamide uptake inhibitors cause rapid toxicity to C6 glioma cells at pharmacologically relevant concentrations.
De Lago E1, Gustafsson SB, Fernández-Ruiz J, Nilsson J, Jacobsson SO, Fowler CJ. J Neurochem. 2006 Oct;99(2):677-88. Epub 2006 Aug 8.
Compounds blocking the uptake of the endogenous cannabinoid anandamide (AEA) have been used to explore the functions of the endogenous cannabinoid system in the CNS both in vivo and in vitro. In this study, the effects of four commonly used acyl-based uptake inhibitors [N-(4-hydroxyphenyl)arachidonylamide (AM404), N-(4-hydroxy-2-methylphenyl) arachidonoyl amide (VDM11), (5Z,8Z,11Z,14Z)-N-(3-furanylmethyl)-5,8,11,14-eicosatetraenamide (UCM707) and (9Z)-N-[1-((R)-4-hydroxybenzyl)-2-hydroxyethyl]-9-octadecen-amide (OMDM2)] and the related compound arvanil on C6 glioma cell viability were investigated. All five compounds reduced the ability of the cells to accumulate calcein, reduced the total nucleic acid content and increased the activity of lactate dehydrogenase recovered in the cell medium. AM404 (10 microm) and VDM11 (10 microm) acted rapidly, reducing cell viability after 3 h of exposure when cell densities of 5,000 per well were used.
2.Oxidative synthesis of highly fluorescent boron/nitrogen co-doped carbon nanodots enabling detection of photosensitizer and carcinogenic dye.
Jahan S1, Mansoor F, Naz S, Lei J, Kanwal S. Anal Chem. 2013 Nov 5;85(21):10232-9. doi: 10.1021/ac401949k. Epub 2013 Oct 17.
Current research efforts have demonstrated the facile hydrothermal oxidative synthetic route to develop highly fluorescent boron/nitrogen co-doped carbon nanodots (CNDs). During this process, N-(4-hydroxyphenyl)glycine served as a source of N doping and a carbon precursor as well, while boric acid H3BO3 is used as an oxidizing agent in the N2 environment. Surface passivation through ultrasonic treatment of CNDs was performed to induce modifications by using various surface passivating agents. Polyethyleneimine (PEI) remarkably enhanced the fluorescence performance and monodispersity of polymerized carbon nanodots (P-CNDs) in aqueous phase with an enhanced quantum yield of 23.71%, along with an increase in size from ~3 nm to ~200 nm. For characterization of CNDs and P-CNDs, UV, infrared, photoluminescence, transmission electron microscopy, x-ray photoelectron spectra, and atomic force microscopy techniques were utilized. Application potentials of synthesized P-CNDs were developed via introduction of protoporphyrin (PPD, a photosensitizer) which has great doping affinity with polymer PEI to switch-off the fluorescence of P-CNDs, leading to the production of dye-doped nanoprobes.
3.4-Hydroxyacetophenone monooxygenase from Pseudomonas fluorescens ACB. A novel flavoprotein catalyzing Baeyer-Villiger oxidation of aromatic compounds.
Kamerbeek NM1, Moonen MJ, Van Der Ven JG, Van Berkel WJ, Fraaije MW, Janssen DB. Eur J Biochem. 2001 May;268(9):2547-57.
A novel flavoprotein that catalyses the NADPH-dependent oxidation of 4-hydroxyacetophenone to 4-hydroxyphenyl acetate, was purified to homogeneity from Pseudomonas fluorescens ACB. Characterization of the purified enzyme showed that 4-hydroxyacetophenone monooxygenase (HAPMO) is a homodimer of approximately 140 kDa with each subunit containing a noncovalently bound FAD molecule. HAPMO displays a tight coupling between NADPH oxidation and substrate oxygenation. Besides 4-hydroxyacetophenone a wide range of other acetophenones are readily converted via a Baeyer-Villiger rearrangement reaction into the corresponding phenyl acetates. The P. fluorescens HAPMO gene (hapE) was characterized. It encoded a 640 amino-acid protein with a deduced mass of 71 884 Da. Except for an N-terminal extension of approximately 135 residues, the sequence of HAPMO shares significant similarity with two known types of Baeyer-Villiger monooxygenases: cyclohexanone monooxygenase (27-33% sequence identity) and steroid monooxygenase (33% sequence identity).
4.Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors.
Alexiou P1, Nicolaou I, Stefek M, Kristl A, Demopoulos VJ. Bioorg Med Chem. 2008 Apr 1;16(7):3926-32. doi: 10.1016/j.bmc.2008.01.042. Epub 2008 Jan 30.
N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamide (4) and its derivatives 5-7 were prepared as putative bioisosteres of the previously reported aldose reductase inhibitors, which are the N-benzenesulfonylglycine derivatives I-IV. The in vitro aldose reductase inhibitory activity of the prepared compounds is higher than that of the respective glycine derivatives. Furthermore, the parent compound 4 reveals high antioxidant potential. Additionally, the intestine permeability of 4 is determined, and there is initial evidence that there is an operating influx mechanism. Overall, the data indicate that the presented chemotype could serve as a core structure for the design of putative pharmacotherapeutic agents, aiming to the long-term complications of diabetes mellitus.