Potent acetylcholinesterase inhibitors: Synthesis, biological assay and docking study of nitro acridone derivatives.
The reaction of o-halobenzoic acid with aniline derivatives and their subsequent cyclization reaction yielded the acridone derivatives. The series of nitro acridone derivatives were prepared by Ullmann condensation in presence of copper as catalyst and were characterized by FTIR, (1)H, (13)C NMR and mass spectra. The structure of 5-nitro-(2-phenyl amino) benzoic acid (4) was confirmed by X-ray crystallography and was found to crystallize in P21/c space group. The in vitro efficacy of the compounds for their acetylcholinesterase (AChE) and antimicrobial inhibitory activities have been evaluated against the standard drugs Ampicillin and Gentamicin against Gram positive and Gram negative bacteria. 1,7-Dinitroacridone was found to be the most potent AChE inhibitor (IC50=0.22μM). Moreover, the compounds have been screened for their antioxidant activity using the DPPH assay. Also, docking study results were found to be in good agreement with the results obtained through in vitro experiments. The docking study further predicted possible binding conformation.
Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: mehtab.organic2009@gmail.com.
Mehtab
M
Parveen
Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
Afroz
A
Aslam
Department of Kulliyat, Faculty of Unani Medicine, Aligarh Muslim University, Aligarh 202002, India.
Shahab A A
SA
Nami
Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
Ali Mohammed
AM
Malla
Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea.
Mahboob
M
Alam
Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea.
Dong-Ung
DU
Lee
Department of Ilmul Advia, Faculty of Unani Medicine, Aligarh Muslim University, Aligarh 202002, India.
Sumbul
S
Rehman
CEMDRX, Physics Department, University of Coimbra, P-3004-516 Coimbra, Portugal.
P S Pereira
PS
Silva
CEMDRX, Physics Department, University of Coimbra, P-3004-516 Coimbra, Portugal.
M Ramos
MR
Silva
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D054831:Acridones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019817:Benzoic Acid / Q000737:chemistry; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D017550:Spectroscopy, Fourier Transform Infrared
D054831:Acridones; D000900:Anti-Bacterial Agents; D002800:Cholinesterase Inhibitors; C041300:acridone; D000667:Ampicillin; D019817:Benzoic Acid; D000110:Acetylcholinesterase
Acetylcholinesterase; Acridone; Antioxidant activity; Docking study