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

Abstract

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, alpha-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 K-i values in the range of 0.23 +/- 0.03-7.12 +/- 0.41 mu M against carbonic anhydrase-I and 0.13 +/- 0.01-6.21 +/- 0.52 mu M against carbonic anhydrase-II. Compounds inhibited acetycholinesterase and butyrylcholinesterase with the K-i 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 alpha-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 K-i values of compounds while the interaction pattern of the current compounds clearly indicates their structure-activity relationship.