ABSTRACT
(E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC50 = 64 µM). Compound 7f was found to be more selective than galanthamine in inhibiting AChE and it showed a moderate selectivity index. Kinetic studies on AChE indicated that a competitive type of inhibition pattern exist for these acrylonitrile derivates. Molecular docking models of the ligand-AChE complexes suggest that compound 7 g is located on the periphery of the AChE active site.
Subject(s)
Acrylonitrile/chemical synthesis , Cholinesterase Inhibitors/chemical synthesis , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Acrylonitrile/analogs & derivatives , Acrylonitrile/chemistry , Cholinesterase Inhibitors/chemistry , Inhibitory Concentration 50 , Kinetics , Molecular Docking Simulation , Protein BindingABSTRACT
18 quinoline-based compounds were tested for antiviral properties against human immunodeficiency syndrome (HIV). The compounds tested here contain quinoline or tetrahydroquinoline rings and can be divided into two main groups: group 1 includes 4-(2-oxopyrrolidinyl-1)-1,2,3,4-tetrahydroquinolines with 2-(3-nitrophenyl) substituent (N-series) or 2-(3-aminophenyl) moiety (H-series), and group 2 includes 2-(3-nitrophenyl)- or 2-(3-aminophenyl)-substituted quinolines (S-series). Two different antiviral assays were performed in order to test the anti-HIV activity of compounds: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and recombinant virus assay (RVA). Results showed that the most active compounds were 2-aryl quinolines, particularly those containing methoxy substituents or no substituents in the quinoline skeleton. HIV transcription inhibition appears to be their target in both resting and phorbol myristate acetate (PMA) activated primary lymphocytes, and nuclear factor-kappaB (NF-kappaB) and specificity protein-1 (SP1) seems to be the most important transcription factors involved in their action.
Subject(s)
Antiviral Agents/pharmacology , HIV/drug effects , NF-kappa B/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Quinolines/pharmacology , Trans-Activators/antagonists & inhibitors , Transcription, Genetic/drug effects , Virus Replication/drug effects , Antiviral Agents/chemistry , Cells, Cultured , Humans , Microbial Sensitivity Tests/methods , Molecular Structure , Quinolines/chemistryABSTRACT
New effective approach to the synthesis of a wide variety of C-2 nitro or aminophenyl substituted quinolines was reported using diverse intermediate 4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines that were prepared by a three component imino Diels-Alder reaction was reported. The key aromatisation process occurs cleanly with the loss of the 2-oxopyrrolinidyl-1 fragment.
