AMINOBENZOIC ACID DERIVATIVES AS ANTIOXIDANTS AND CHOLINESTERASE INHIBITORS; SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDIES

摘要

Cholinesterase namely, acetyl- and butyrylcholinesterase (AChE and BChE, respectively), has been recognized as a primary class of enzyme that hydrolyzes the acetylcholine (ACh) neurotransmitter in synaptic junctions. Diminished levels of the neurotransmitter in synaptic junction lead to Alzheimer's disease (AD). Inhibition of cholinesterase is thus, an attractive strategy for AD treatment. The study includes the synthesis and characterization of a series of 2-, 3- and 4-aminobenzoic acid derivatives (1a-5c), their biological screening against cholinesterase enzyme and molecular docking study to demonstrate putative binding modes. Antioxidant potential of the synthesized series was also determined. The cholinesterase enzyme inhibition assay showed that compound 5b has the highest inhibition potential against acetylcholinesterase with an IC50 value of 1.66 +/- 0.03 mu M while in case of butyrylcholinesterase, compound 2c has the highest inhibitory potential with an IC50 value of 2.67 +/- 0.05 mu M. Molecular docking studies supports the results of enzyme inhibition potential with binding energy value Delta G = -9.54 Kcal mol(-1) for compound 5b in case for acetylcholinesterase while for butyrylcholinesterase, Delta G = -5.53 Kcal mol(-1) was obtained for compound 2c. The synthesized series of compounds also shows mild to moderate antioxidant potential. The benzoyl- containing compounds shows better antioxidant activity as compared to other derivatives of the synthesized series. Based on the molecular docking studies and enzyme inhibition potential, the synthesized series of compounds can be regarded as potent cholinesterase inhibitors and can be used for designing and synthesizing more potent drugs for Alzheimer's disease and neurodegenerative diseases.