Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Monoamine oxidase-B (MAO-B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) have been considered target enzymes of depression and neurodegenerative diseases, including Alzheimer's disease (AD). In this study, seventeen -methyl-piperazine chalcones were synthesized, and their inhibitory activities were evaluated against the target enzymes. Compound (3-trifluoromethyl-4-fluorinated derivative) showed the highest selective inhibition against MAO-B with an IC of 0.71 μM and selectivity index (SI) of 56.34, followed by (2-fluoro-5-bromophenyl derivative) (IC = 1.11 μM, SI = 16.04). Compounds and were reversible competitive MAO-B inhibitors with K values of 0.21 and 0.28 μM, respectively. Moreover, and effectively inhibited AChE with IC of 8.10 and 4.32 μM, which underscored their multi-target inhibitory modes. Interestingly, compound elicited remarkable inhibitions over MAO-B, AChE, and BChE with IC of 1.19-3.87 μM. A cell-based assay of compounds and against Vero normal cells pointed out their low cytotoxicity. In a docking simulation, showed the lowest energy for MAO-B (-11.6 kcal/mol) with four hydrogen bonds and two π-π interactions. Furthermore, in silico studies were conducted, and disclosed that and are expected to possess favorable pharmacokinetic properties, such as the ability to penetrate the blood-brain barrier (BBB). In view of these findings, compounds and could serve as promising potential candidates for the treatment of neurodegenerative diseases.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860728 | PMC |
http://dx.doi.org/10.3390/ph16010083 | DOI Listing |
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