title: Active site directed docking studies: synthesis and pharmacological evaluation of cis-2,6-dimethyl piperidine sulfonamides as inhibitors of acetylcholinesterase.
abstract: Hypocholinergic function associated with Alzheimer's disease (AD) is well-accepted hypothesis, in this regard, many research attempts have been made to elevate the reduced cholinergic neurotransmission, among them two main treatment strategies were widely explored, namely stimulation of muscarinic receptor 1 and/or reversible inhibition of acetylcholinesterase (AChE) enzyme. In an attempt to improve the efficacy and to minimize general side effects of these AChE inhibitors, many lead molecules are developed in research; one among them is piperidine derivative. Donazepil is a widely prescribed AChE inhibitor which displays a piperidine ring in its structure. In the present study, we have docked cis-2,6-dimethyl piperidine sulfonamides (3a-i) on AChE enzyme and synthesized by nucleophilic substitution reaction between cis-2,6-dimethyl piperidine and alkyl/aryl sulfonyl chlorides in the presence of triethylamine. These piperidine sulfonamides were subjected to in vitro AChE enzyme inhibition studies and in vivo antiamnesic study to reverse scopolamine induced memory loss in rats. Two derivatives (3a and f) in this class of piperidines (3a-i) showed considerable inhibition against different sources of AChE in vitro and reduced average number of mistakes done by wistar rats as compared to scopolamine treated group in vivo (rodent memory evaluation).
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore - 570006, Karnataka, India.
authors.forename: H R
authors.initials: HR
authors.lastname: Girisha
authors.forename: J N
authors.initials: JN
authors.lastname: Narendra Sharath Chandra
authors.forename: Sriramamurthy
authors.initials: S
authors.lastname: Boppana
authors.forename: Manish
authors.initials: M
authors.lastname: Malviya
authors.forename: C T
authors.initials: CT
authors.lastname: Sadashiva
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D010880:Piperidines; D013449:Sulfonamides; D000110:Acetylcholinesterase