RESUMO
(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.
Assuntos
Acrilonitrila/síntese química , Inibidores da Colinesterase/síntese química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Acrilonitrila/análogos & derivados , Acrilonitrila/química , Inibidores da Colinesterase/química , Concentração Inibidora 50 , Cinética , Simulação de Acoplamento Molecular , Ligação ProteicaRESUMO
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.
Assuntos
Antivirais/farmacologia , HIV/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Quinolinas/farmacologia , Transativadores/antagonistas & inibidores , Transcrição Gênica/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Antivirais/química , Células Cultivadas , Humanos , Testes de Sensibilidade Microbiana/métodos , Estrutura Molecular , Quinolinas/químicaRESUMO
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.