Synthesis, Characterization, and Evaluation of Difluoropyrido[4,3-b]indoles as Potential Agents for Acetylcholinesterase and Antiamnesic Activity.
Acetylcholinesterase (AChE) inhibitors are currently the most widely prescribed drugs for Alzheimer's disease. The high potential of indole compounds in medicinal chemistry led us to discover a novel series of fluoroindole compounds. The synthesis and pharmacological analysis of the difluoropyrido[4,3-b]indoles 11-34 are described. Compounds 11-34 were tested for AChE inhibition activity using a rat brain homogenate. Compounds 25-29 display a promising in vitro profile with an IC50value range of 46-51.6 nM and show significant protective effect on scopolamine-induced amnesia. The present data indicate that compounds 25-29 may represent attractive potent molecules for the treatment of Alzheimer's disease.
Department of Chemistry, University of Mysore, Manasagangothri Mysore, Karnataka, India.
Malavalli
M
Madaiah
Department of Chemistry, B.N.M. Institute of Technology, Bengaluru, Karnataka, India.
Bidarur K
BK
Jayanna
Department of Civil Engineering, B.N.M. Institute of Technology, Bengaluru, Karnataka, India.
Arakere S
AS
Manu
Department of Chemistry, B.N.M. Institute of Technology, Bengaluru, Karnataka, India.
Maralekere K
http://orcid.org/0000-0001-8526-9241
MK
Prashanth
Department of Chemistry, University of Mysore, Manasagangothri Mysore, Karnataka, India.
Hosakere D
HD
Revanasiddappa
Department of Pharmacology, G Pullareddy College of Pharmacy, Mehdipatnam, Hyderabad, India.
Bantal
B
Veeresh
D000110:Acetylcholinesterase / Q000378:metabolism*; D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D016466:CHO Cells; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D002243:Carbolines; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase
Acetylcholinesterase; Alzheimer's disease; Antiamnesic activity; Difluoropyrido[4,3-b]indoles