Central nervous system agents in medicinal chemistry最新文献

{"title":"Thiazolidine: A Potent Candidate for Central Nervous Systems Diseases.","authors":"Radhe Shyam Bahare, Swastika Ganguly, Ritesh Agrawal, Subodh Narayan Dikshit","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Thiazolidines are multifaceted molecules and exhibit varied types of biological activities, and also showed anticonvulsants and antidepressants activity. It is the diversified class of heterocyclic compounds. Thiazolidinediones (TZD) has been shown beneficial action in various CNS diseases. The significant mechanism of TZD-induced neuroprotection useful in prevention of microglial activation and cytokine that is responsible for inflammatory condition and chemokine expression. At the molecular level TZDs were also responsible to prevent the activation of pro-inflammatory transcription factors as well as promoting the anti-oxidant mechanisms in the injured CNS. Important SAR, molecular mechanism and potent biological activities with special references to central nervous system are discussed in this article. Various investigations suggest that this moiety pave the way for design and discovery of new drug candidates.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2016-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand based drug design of new heterocyclic imines of GABA analogues: A molecular docking approach for the discovery of new GABA-AT inhibitors.","authors":"Bijo Mathew, Githa Elizabeth Mathew, Jerad Suresh, Dhasthakeer Usman, Puthucode Natarajan Shiva Subramanyan, Kallivalappil Fathima Safna","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is mainly catalysed by GABA aminotransferase (GABA-AT), excessive activity of which leads to convulsions. Inhibition of GABA-AT increases the concentration of GABA and can terminate the convulsions. Several studies have revealed that GABA analogues could be the outstanding scaffolds for the design of potent inhibitors of GABA-AT. The poor ability of GABA analogues to cross the blood-brain barrier (BBB), always produces low therapeutic index. However, Vigabatrin, a mechanism-based inhibitor of GABA-AT, is currently approved treatment of epilepsy, but it has harmful side effects, leaving a need for improved GABA-AT inactivators.</p><p><strong>Experimental design: </strong>In our present in silico investigation, AutoDock 4.2,-based on Lamarckian genetic algorithm was employed for virtual screen of a compound library with 35 entries (Schiff's bases of GABA) in search for novel and selective inhibitors of GABA-AT.</p><p><strong>Results: </strong>By means of flexible type of molecular docking, we proposed that these designed molecules could successfully bind into the active pocket of GABA-AT with good predicted affinities in comparison to standard vigabatrin. Among the designed analogues, HIG18, HIG28 and HIG30 showed significant binding free energy of -10.25, -9.88 and -9.31 kcal/mol with predicted inhibitory constant values of 0.03, 0.05 and 0.15 µM respectively.</p><p><strong>Conclusion: </strong>Using ligand-based drug design, we proposed that electron withdrawing phenyl substituted heterocyclic imines of GABA could be considered as promising structures for synthesis and testing of new GABA-AT inhibitors from this class. We hypothesize that novel GABA analogues with an azomethine linkage incorporated with heterocyclic system can have increased affinity and more lipophilic character that would provide a probability of having less toxic effect in the therapy of convulsions.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2016-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}