The Pharmacology of Excitotoxins and Energy Deprivation in Hippocampal Slices
Avital Schurr, Benjamin M. Rigor in BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
To test the ability of the energy-deprived rat hippocampal slice preparation as a potential drug screening system, two groups of compounds were chosen: five pyridine dicarboxylate derivatives (3,4-PDA, 2,4-PDA, 2,5-PDA, 2,6-PDA, and 6-Me-QUIN) and three heterocyclic dicarboxylates (IZDA, TZDA, and PZDA). The excitotoxicity of these compounds was compared to that of QUIN. The five pyridine dicarboxylates are compounds differing from one another only in the positions of the two carboxylic groups on the pyridine ring or in the inclusion of a methyl group on that ring (Figure 1). The heterocyclic compounds all have two carboxylic groups, either in positions 2 and 3 or in positions 4 and 5, always adjacent to a nitrogen atom in the heterocyclic ring (Figure 1).
Antiplatelet Therapy
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
Many compounds of this group, most of which are derived from pyridine5,55 or imidazole,56,57 are available. To date, the compound most studied in man is dazoxiben acid. The expected inhibition of thromboxane synthesis was achieved ex vivo but was short lived. Bleeding time and platelet aggregation were only minimally impaired.56,59,60 The first clinical trials were disappointing. This may be explained by accumulation of platelet endoperoxides replacing thromboxane. As such, platelet behavior is less impaired than with aspirin.62,63 Another explanation is the fact that the degree of metabolic diversion towards prostacyclin is, in fact, slight and of minor importance relative to the proaggregating formation of prostaglandin E2 by the platelet.63,64
Effects of solar radiation, air pollution, and artificial blue light on the skin
Roger L. McMullen in Antioxidants and the Skin, 2018
Elastin, found in the dermis, provides skin with elastic properties. Cross-links exist within the protein structure that help to maintain its elastic nature, preventing indefinite extension of the elastic fibers. The cross-links are formed between lysine residues with the amino acid desmosine (Figure 4.6) and its isomer, isodesmosine. Due to the pyridinium ring in desmosine and isodesmosine, absorption occurs in the UVB and UVA region of the spectrum, lending to its ability to act as a photosensitizing agent. Similarly, cross-linking of collagen in the dermis is due to the amino acid, pyridinoline, which displays similar photochemical behavior as the desmosine isomers (Figure 4.6). Further, as a result of UV-induced damage, advanced glycation end products are produced in the extracellular matrix (ECM). This results in cross-links that are produced by pyridinium compounds, such as glycol-aldehyde pyridine. Other pyridine containing compounds are found in skin, many of which may act as photosensitizing agents by absorbing UVA radiation.7,8
Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Roberta Pacifico, Nunzio Del Gaudio, Guglielmo Bove, Lucia Altucci, Lydia Siragusa, Gabriele Cruciani, Menotti Ruvo, Rosa Bellavita, Paolo Grieco, Mauro F. A. Adamo
As a follow up of this work, we have posed the question of whether or not those classes of new compounds may be useful in medicinal chemistry. Triazoles were repeatedly reported as bioactive compounds1–11 and many drug candidates containing the pyridine ring were equally described. Pyridines are commonly used in medicinal chemistry because of their ability to establish hydrogen bonds either as donors or acceptors, their water solubility, small dimensions and, most importantly, their potential to act as amide bioisosteres13. The latter in particular, makes pyridine pivotal in drug discovery14. Additionally, if compared to the benzene ring15–17, the pyridine unit displays a relevant increased basicity18, an improved aqueous solubility19 and a smaller polar surface; 20; all of these features consent an optimal orientation of the pyridine-containing drugs with the biological target through π-stacking interactions21,22. According to the FDA23, there are more than 95 approved drugs containing the pyridine moiety that are, currently, employed against tuberculosis (i.e., isoniazid24,255 and ethionamide266), HIV/AIDS (i.e., delavirdine277), Alzheimer disease (i.e., tacrine288), Raynaud’s syndrome (i.e., nifedipine299), hypertension (e.g., nivaldipine3010) and so on among the others (Figure 1).
Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Bo Qin, Qian Bai, Dan Yan, Fanxiang Yin, Zhu Zhu, Chaoyuan Xia, Yang Yang, Yi Zhao
1,2,3-Triazole as one of the most important classes of nitrogen-containing heterocycle exhibits potent anticancer activity6. 1,2,3-triazole-benzoxazole hybrid 1 (Figure 1) displayed antiproliferative activity against SKBr3, HepG2, and HeLa cells with IC50 values of 7.1, 11.2, and 6.8 μg/mL7. 1,2,3-Triazole-benzisoxazole hybrid 2 showed antiproliferative activity against MOLM13, MOLM14, and MV4-11 cell lines8. Hybrid 3 inhibited migration and mammosphere formation and induced cell cycle arrest at G2-M phase against breast cancer cells9. On the other hand, pyridine derivatives also have a wide-range of therapeutic applications in the area of drug discovery10. Pyridine analogue FTO-IN-5 (Figure 1) as a selective FTO inhibitor could decrease the viability of acute monocytic leukaemia cells and increase the level of N6-methyladenosine in mRNA11. Pyridine analogue FTO-IN-6 selectively inhibited FTO and formed hydrogen bonds with residues Ser318 and Tyr29512.
Hematotoxic, oxidative and genotoxic damage in rainbow trout (Oncorhynchus mykiss) after exposure to 3-benzoylpyridine
Published in Toxicology Mechanisms and Methods, 2022
Veysel Parlak, Bünyamin Ozgeris, Arzu Ucar, Aslı Cilingir Yeltekin, Fatma Betul Ozgeris, Ozge Cağlar, Gonca Alak, Hasan Turkez, Muhammed Atamanalp
Pyridine is used as an important reagent and solvent for pesticide. Pyridine derivatives are used in many different fields such as pesticides, vitamins, food sweeteners, paints, rubber products and adhesives as well as industrial solvents (Mathur et al. 2008). The pyridine is a hetero-aromatic compound that has a nitrogen atom instead of the carbon atom of a benzene molecule. The compounds containing pyridine ring have toxicological significance. A number of compounds having pyridine ring exhibited therapeutic potentials including antihistamine, antibacterial, anticholinergic features (Hamada 2018). However, toxicity data of 3-benzoylpyridine (3BP) in the ketone groups is so limited. In this sense, the assessment of biochemical changes caused by these chemicals on living organisms is critically important. Moreover, 3BP was reported to increase the generation of reactive oxygen species (ROS) in living organisms and give rise to non-target influences like stimulation of cell death via cellular oxidation process in a recent investigation (Parlak 2018). Therefore, the aim of the research was to evaluate the effects of 3BP on the AChE activity, 8-OHdG level, Caspase-3 activity, antioxidant enzyme activities [(superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase (PON) and arylesterase (AR)] as well as hematological index and genotoxicity end-point (MN rates) in O. mykiss’ brain, liver, gill and blood tissues.