Synthesis, Characterization, Bioactivity Impacts of New Anthranilic Acid Hydrazones Containing Aryl Sulfonate Moiety as Fenamate Isosteres

• Published in: ChemistrySelect (Weinheim) Vol. 8; no. 13
• Main Authors: Tokalı, Feyzi Sinan, Taslimi, Parham, Sadeghian, Nastaran, Taskin‐To, Tugba, Gülçin, İlhami
• Format: Journal Article
• Language: English
• Published: 05.04.2023
• Subjects: Anti-cholinesterase; anti-diabetic; fenamate isosteres; molecular docking; synthesis
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202300241

In this study, it was planned to synthesize new members of fenamate isosteres and investigate its effect on some metabolic enzymes such as Acetylcholinesterase, Butyrylcholinesterase, α‐Glucosidase, Carbonic andyhrase I–II. The target compounds were obtained from the reaction of N‐subtituted anthranilic hydrazides with sulfonylated aldehyde derivatives. The structures of the compounds were characterized using Fourier‐transform Infrared, Nuclear Magnetic Resonance, and High‐resolution Mass Spectroscopy. Compounds had potent inhibitory strength with Ki values in the range of 0.23±0.03–7.12±0.41 μM against carbonic anhydrase‐I and 0.13±0.01–6.21±0.52 μM against carbonic anhydrase‐II. Compounds inhibited acetycholinesterase and butyrylcholinesterase with the Ki values in the range of 42.73±15.80 nM–977.52±32.67 nM and 25.84±4.09 nM–261.36±34.05 nM, respectively. All compounds showed potent inhibitory activity against α‐glucosidase enzyme with IC50 value 1.51–23.51 nM, compared to the standard acarbose (64.53 nM). The orientation of binding of the synthesized compounds were further appraised by molecular docking studies, which reflects the importance of sulfonyl, furan, thiophene, and methoxy groups in protein‐ligand interaction. The docking results are complementary with the Ki values of compounds while the interaction pattern of the current compounds clearly indicates their structure‐activity relationship. A series of new fenamate isosteres were synthesized to investigate their inhibitory properties against some metabolic enzymes such as AChE, BChE, hCA I–II, and α‐Glu. Compound 4 for AChE and BChE, compound 11 for hCA I–II and compound 9 for α‐Glu are the most effective compounds. Molecular docking study was also performed to understand the interactions between ligands and the current enzymes.