30377-27-6Relevant articles and documents
Design and development of novel thiazolidin-4-one-1,3,5-triazine derivatives as neuro-protective agent against cerebral ischemia–reperfusion injury in mice via attenuation of NF-?B
Lu, Min,Qi, Yujun,Han, Yu,Yi, Qiong,Xu, Lei,Sun, Wenlin,Ni, Guihua,Ni, Xiaoyu,Xu, Changsong
, p. 1315 - 1327 (2020/07/13)
The present study enumerates the discovery and development of novel thiazolidin-4-one-1,3,5-triazine as neuro-protective agent against cerebral ischemia–reperfusion injury in mice. These compounds showed significant inhibition of NF-?B transcriptional activity in LPS-stimulated RAW264.7 cells, displaying compound 8k as most potent inhibitor among the tested derivative. The compound 8k was further studied in in vivo middle cerebral artery occlusion (MCAO) mice model for neuro-protective action. Results suggest that compound 8k causes attenuation of inflammation (TNF-α, IL-β, and IL-6), oxidative stress (SOD, GSH, and MDA), and apoptosis (Bcl-2, Bax, and cleaved caspase-3) in MCAO mice in concentration-dependent manner. Collectively, our results documented that compound 8k pre-treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro-protective agent by inactivation of NF-?B.
Tailoring the Substitution Pattern on 1,3,5-Triazine for Targeting Cyclooxygenase-2: Discovery and Structure-Activity Relationship of Triazine-4-Aminophenylmorpholin-3-one Hybrids that Reverse Algesia and Inflammation in Swiss Albino Mice
Singh, Palwinder,Kaur, Sukhmeet,Kumari, Priya,Kaur, Baljit,Kaur, Manpreet,Singh, Gurjit,Bhatti, Rajbir,Bhatti, Manpreet
, p. 7929 - 7941 (2018/09/06)
Here, we report analgesic and anti-inflammatory activity of a series of compounds obtained by appending 4-aminophenylmorpholin-3-one and acyclic, cyclic, or heterocyclic moieties on 1,3,5-triazine. The structures of compounds 4b and 6b are optimized for the best inhibition of COX-2 with IC50 values of 0.06 and 0.08 μM, respectively, and selectivity over COX-1 of 166 and >125, respectively. At the dose of 5 mg kg-1, these compounds significantly reduced acetic acid induced writhings, and their ED50 values were found to be 2.2 and 1.9 mg kg-1, respectively. Besides the cell-based and animal-based experiments showing the modes of action of these compounds targeting COX-2, the interaction behavior of 4b with COX-2 was also characterized, with physicochemical experiments including ITC, NMR, UV-vis, and molecular-modeling studies. Characteristically, these compounds interact with R120, Y355, and W385, the residues responsible for holding the substrate and mediating the process of electron transfer during the metabolic phase of the enzyme.
Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents
Jameel, Ehtesham,Meena, Poonam,Maqbool, Mudasir,Kumar, Jitendra,Ahmed, Waqar,Mumtazuddin, Syed,Tiwari, Manisha,Hoda, Nasimul,Jayaram
, p. 36 - 51 (2017/05/09)
In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC50 values 0.065 and 0.092?μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ～28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy.
